Obeticholic acid (OCA) is the second-line therapy for primary biliary cholangitis (PBC), as well as an attractive candidate as a treatment for metabolic dysfunction-associated steatohepatitis (MASH). This meta-analysis aims to assess the impact of OCA on lipid profiles and clinical outcomes in patients with PBC and MASH. A comprehensive systematic review and meta-analysis of randomized controlled trials (RCTs) from five major databases were conducted. Changes in lipid profiles from baseline were compared between groups receiving placebo and OCA. Efficacy outcomes were evaluated separately for PBC and MASH trials, while safety outcomes included pruritus, gastrointestinal disturbances, and headache. OCA treatment exhibited a significant increase in low-density lipoprotein cholesterol (LDL-C) (standardized mean difference [SMD] = 0.39; 95 % confidence interval [CI] = 0.15 to 0.63) and a decrease in high-density lipoprotein cholesterol (HDL-C) (SMD = −0.80; 95 % CI = −1.13 to −0.47) in both PBC and MASH patients compared to placebo. OCA demonstrated superior efficacy to placebo in treating PBC and MASH, evident in both primary and secondary outcomes. The incidence of pruritus was significantly higher with OCA compared to placebo (risk ratio = 1.78, 95 % CI = 1.42 to 2.25). OCA is more efficacious than a placebo in the treatment of PBC and MASH. However, caution is needed given the association of OCA use with a significant increase in LDL-C levels and a decrease in HDL-C levels among patients with these conditions.