Objectives: As a severe mental health condition, schizophrenia presents a chronic and complex clinical manifestation and neuropathology. A large body of literature exists on the pharmacological treatment of schizophrenia. However, evidence on some dimensions of such interventions (e.g., eligible candidates, potential predicting factors of the therapeutic outcomes, safe implementation of these interventions, etc.) are notably scarce. Studies revealed superior influences of adjunct statin therapy over placebo among patients with schizophrenia. The study aimed to investigate the effects of aspirin and simvastatin as adjunctive therapy, compared to placebo on positive and negative symptoms and general psychopathology of patients with schizophrenia. Methods: This is a double-blind, randomized clinical trial. The sample size was estimated to be 15 individuals for each one of the three research groups (n=45). The Positive And Negative Syndrome Scale (PANSS) and the Hamilton Rating Scale For Depression (HAM-D) were employed to collect the study data in the present study. The study patients were recruited from patients admitted to the psychiatric wards of Razi Hospital were identified. The study subjects were randomly divided into two test groups and one control group. All groups were initially treated with risperidone 4 mg daily for 3 weeks. Then, group A received aspirin (325 mg twice daily), whereas group B was prescribed 40 mg/d of simvastatin. However, the control group received a placebo. Psychiatric symptoms were recorded according to the PANSS at the beginning of the study and then at weeks 4 and 8. The results were analyzed using inferential statistics (repeated-measures analysis of covariance) and descriptive statistics in SPSS software v. 20. Results: Of 45 patients, 35(77.78%) were men (Mean±SD age: 45.8±10.5 years), and 10(22.23%) were women (Mean±SD age: 42.3±7.8 years). The mean scores of the positive symptoms of PANSS significantly decreased in the groups treated with aspirin and simvastatin (P=0.006 and P=0.005, respectively). However, no such difference was seen in the controls (P=0.447). Furthermore, the mean scores of the negative symptoms of PANSS significantly decreased in the intervention groups (P<0.001); in addition, no significant differences were seen in the controls after the end of the research program (P=0.18). In addition, the mean scores of the general symptoms of PANSS significantly decreased in the aspirin and simvastatin groups (P<0.001). There was an increase in the same value in the controls, but the increase was not significant (P=0.31). Finally, while the total mean scores of the PANSS increased in the control group (P=0.25), the corresponding scores significantly decreased in the test groups receiving aspirin and simvastatin (P<0.001). Discussion: The present study results indicate that either aspirin or simvastatin can reduce the symptoms of schizophrenia, including general psychopathology, negative symptoms, and positive symptoms in the explored patients. Also, the effectiveness of both drugs was similar, and no significant difference was detected between these medications in reducing the symptoms mentioned above.