Schizophrenia is one of many psychotic disorders on a broad spectrum. The symptoms of psychosis resulting from schizophrenia and other spectrum disorders are treated with several medications, including aripiprazole, clozapine, risperidone, etc. However, these drugs are associated with adverse effects. This study was conducted to evaluate histological and biochemical changes linked to the blockage of serotonin receptors caused by risperidone and aripiprazole. Fifteen Sprague Dawley albino rats were divided into three groups of five rats each. Group 1 served as the control and received a placebo (normal saline), Group 2 received risperidone (20 mg/kg/day), and Group 3 was given aripiprazole (10 mg/kg/day). After three months of treatment, a biochemical analysis of liver enzymes was performed, followed by a histological examination. The results revealed that the architecture of the liver cells appeared normal in all three groups. However, when risperidone and aripiprazole treatment groups were compared to the control group, histology was slightly altered. The level of glutamic oxaloacetic transaminase (GOT) in the control group increased slightly from 70 to 75 U/L. GOT levels increased from 80 to 120 U/L and 130 to 140 U/L in the aripiprazole and risperidone groups, respectively. A similar observation was made for the levels of glutamate pyruvate transaminase (GPT) and alkaline phosphatase (ALP) compared to the control group. The findings of this study found the levels of the biochemical enzymes within safe limits with the administration of aripiprazole and risperidone. However, patients using these drugs should always have routine laboratory examinations for liver enzyme tests.