Background The current comparative efficacy, safety, and acceptability of atypical antipsychotics (AAPs) in treating Parkinson's Disease Psychosis (PDP) are not entirely understood. Objective To evaluate comparative efficacy, safety, and acceptability of AAPs in patients with PDP. Methods We conducted a systematic review and a network meta-analysis to compare the efficacy, safety, and acceptability of pimavanserin, quetiapine, olanzapine, clozapine, ziprasidone, and risperidone. We estimated relative standardized mean differences (SMDs) for continuous outcomes and odds ratios (OR) for binary outcomes, with their respective 95% confidence intervals (CIs). Results We included 19 unique studies evaluating AAPs in a total of 1,242 persons with PDP. Based on Clinical Global Impression Scale for Severity, pimavanserin (SMD, −4.81; 95% CI, −5.39, −4.24) and clozapine (SMD, −4.25; 95% CI, −5.24, −3.26) significantly improved symptoms compared with placebo. Also, compared to placebo, pimavanserin (OR, 1.16; 95% CI, 1.07, 1.24) significantly improved psychotic symptoms based on Scale for Assessment of Positive Symptoms for Parkinson's Disease Psychosis/Hallucinations and Delusions scores. In comparison to placebo, clozapine (SMD, −0.69; 95% CI, −1.35, −0.02), pimavanserin (SMD, −0.01; 95% CI, −0.56, 0.53), and quetiapine (SMD, 0.00; 95% CI, −0.68, 0.69) did not impair motor function per Unified Parkinson's Disease Rating scale. Based on Mini-Mental State Examination scale, quetiapine (SMD, 0.60; 95% CI, 0.07, 1.14) significantly impaired cognition compared to placebo. Conclusions In patients with PDP, pimavanserin and clozapine demonstrated significant improvement in psychosis without affecting motor function. With quetiapine being associated with a significant decline in cognition and despite not impairing motor function, our findings suggest that it should be avoided in patients with PDP and reduced cognitive abilities.