Hepatocyte injury is assessed by serum aspartate transaminase and alanine transaminase estimation. In psychiatric populations, antipsychotic drugs (AD) are culprit in hepatic dysfunction. The objective of the current work is to assess transaminitis among psychiatric patients treated by AD. Methods: This cross-sectional study was conducted in Zagazig University Hospitals in Egypt, from December 2022 to February 2023. A total of 135 adult patients aged ≥ 18 years, were diagnosed with psychiatric disorders after the exclusion of patients receiving any hepatotoxic drugs, viral hepatitis, having chronic liver or kidney diseases, diabetes mellitus, mental retardation, and pregnant females. Results: Among the 135 patients, 104 (77.0%) were males. Their age was 32 ± 9, The most popular used class of AD was atypical AD 84 (62.2%). The overall incidence of transaminitis among patients receiving AD was 23/135 (17.04%) of patients; 13 (56.5%) were on atypical AD compared to 10 (43.5%) patients receiving combined AD, without any statistically significant difference. Conclusions: The use of AD in patients with psychiatric disorders is potentially safe with minimal transaminitis (<one-fold elevation). However, baseline and regular monitoring of serum aminotransferase is recommended during treatment.