Inclusion Criteria:
* Known diagnosis of histologically-confirmed BE with either no dysplasia, indefinite for dysplasia, or low-grade dysplasia as defined by the presence of specialized columnar epithelium on histology and \>= 2 cm of involvement on endoscopy
* Adequate Barrett's mucosa, which is defined as at least one sample with \>= 50% intestinal metaplasia in biopsies required to satisfy the endpoints of the study
* Participants are on proton pump inhibitors (PPI) therapy for \>= 28 days duration
* Age \>= of 18 years. Because no dosing or adverse event (AE) data are currently available on the use of OCA in participants \< 18 years of age, children are excluded from this study but will be eligible for future pediatric trials, if applicable
* Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 70%)
* Hemoglobin \>= 10g/dL or hematocrit \>= 30 %
* Leukocyte count \>= 3,500/microliter
* Platelet count \>= 100,000/microliter
* Creatinine clearance (calculated if measured is not available) \>= 30mL/min/1.73m\^2
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 1.5 X institutional upper limit of normal (ULN)
* Total bilirubin =\< 1.0 X ULN
* Alkaline phosphatase =\<1.5 X ULN
* Gamma-glutamyl transferase (GGT) =\< 1.5 X ULN
* The effects of OCA on the developing human fetus are unknown. For this reason, all men and women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, throughout the duration of study participation, and for at least 6 months after receiving the last dose of study drug. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately
* Ability to understand the study procedures, benefits and risks, and sign a written informed consent document. Non-English speaking participants are allowed to enroll even if they skip answering quality-of-life (QOL) questionnaires. Special efforts will be made through community advisory boards at participating sites to reach Spanish speaking participants
* Willing to undergo testing for human immunodeficiency virus (HIV) testing if not tested within the past 6 months
* Willing to undergo hepatitis B and C screening if not tested within the past 6 months
* Willing and able to adhere to the prohibitions and restrictions specified in the approved protocol
* Willingness to moderate alcohol intake (consuming no more than 1 or 2 alcoholic drinks per day for women and men, respectively)
* Participants must have no evidence of active or recurrent invasive cancer for 6 months prior to screening and must be at least 6 months from any prior cancer-directed treatment (such as surgical resection, chemotherapy, immunotherapy, hormonal therapy or radiation)
Exclusion Criteria:
* History of prior ablative therapy such as radiofrequency ablation, cryotherapy or argon plasma coagulation (APC) in BE segment
* Prior use of OCA
* Prior history or presence of high-grade disease (HGD) or cancer on pre-intervention endoscopy
* Cutaneous diseases manifesting with severe pruritus
* Individuals with active, known or suspected chronic liver disease including cirrhosis, nonalcoholic steatohepatitis (NASH) with fibrosis or cirrhosis, primary sclerosing cholangitis, biliary atresia
* Individuals with acute cholecystitis (defined by a syndrome of right upper quadrant pain, fever, and leukocytosis associated with gallbladder inflammation)
* Individuals with a history of pancreatitis or pancreatic abnormalities
* Individuals with hepatic steatosis and velocity \> 1.7 m/sec as determined by liver ultrasound elastography. Results of a right upper quadrant ultrasound with elastography performed within 6 months of starting study treatment may be used to assess this criteria
* Individuals with hyperlipidemia that is not well controlled with the use of pharmacotherapy and/or dietary modifications
* History of severe, progressive, or uncontrolled renal, genitourinary, hepatic, hematologic, endocrine, cardiac, vascular, pulmonary, rheumatologic, neurologic, psychiatric, or metabolic disturbances, or signs and symptoms thereof
* Individuals with known hypersensitivity, allergies, or intolerance to the study drug or compounds of similar chemical or biologic composition
* Any serious and/or unstable pre-existing medical disorder (aside from malignancy exception above), psychiatric disorder, or other conditions that could interfere with participant's safety, obtaining informed consent, or compliance to the study procedures
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
* Individuals with active and untreated hepatitis C virus (HCV) and/or or hepatitis B virus (HBV) infection
* Individuals with HIV infection are eligible for participation if:
* CD4+ count \>= 300/uL
* Viral load is undetectable
* Receiving highly active antiretroviral therapy (HAART) without known or suspected drug interactions with OCA
* Consultation with the participant's infectious disease specialist may be obtained
* Individuals taking the drugs listed below may not be randomized unless they are willing to stop the medications (and possibly change to alternative non-excluded medications to treat the same conditions) no less than 5 half-lives days prior to starting OCA or placebo on this study. Consultation with the participant's primary care provider may be obtained but is not required.
* The use of the following drugs or drug classes is prohibited during OCA/placebo treatment
* Investigational agents;
* Bile acid sequestrants (bile acid binding resins): cholestyramine, colestipol, or colesevelam;
* Bile salt efflux pump (BSEP) inhibitors;
* Clozapine;
* Theophylline derivatives;
* Tizanidine;
* Warfarin;
* Hepatotoxic drugs such as amiodarone, sodium valproate, certain herbal/dietary supplements, and long-term doxycycline or tetracycline
* Pregnant, breast-feeding, or women of childbearing potential unwilling to use a reliable contraceptive method. Pregnant women are excluded from this study because OCA is an agent with unknown effects on the developing human fetus. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with OCA, breastfeeding should be discontinued if the mother is treated with OCA
* Participants may not be receiving any other investigational agents
