Background: Metformin (MET) has been used to prevent weight gain in patients treated with antipsychotic drugs. However, liraglutide (LIRA), initially used for diabetes, is now considered for obesity treatment. The aim of this study was to investigate the effectiveness and safety of these drugs in patients with psychiatric disorders. Methods: A retrospective chart review was performed on patients prescribed and administered MET and LIRA from January 1, 2017 to August 31, 2023. To assess treatment efficacy, the mean change in the body mass index of the patients before and after drug use was calculated for both medications. Drug safety was evaluated by determining the early discontinuation and occurrence of adverse effects. Results: We collected data from 45 patients, with the majority being women (84.4%). The most frequently diagnosed psychiatric disorders were depressive disorder for LIRA (35.3%) and psychotic disorder for MET (63.6%). No demographic variations were observed between patients who were administered the two types of drugs. The treatment efficacy and safety of both drugs did not show any statistically significant difference. When conducting a subgroup analysis exclusively on patients diagnosed with psychotic disorders (n = 14), MET showed better efficacy; however, no statistically significant difference was observed (−2.48±3.17 vs. 0.56±2.93, t=−1.860, p=0.088). Conclusion: LIRA and MET did not show any significant differences in terms of therapeutic efficacy and safety. However, in patients diagnosed with psychotic disorders, MET showed better efficacy and was cost-effective than LIRA. Future studies with larger sample sizes are required to confirm these findings.