We aimed to assess the effects of olanzapine in the improvement of body weight and appetite in patients with cancer or receiving chemotherapy through a systematic review and meta-analysis. We searched the following databases from their inception to April 23, 2024: Embase, PubMed, Web of Science, and the Cochrane Library. The mean difference (MD) and risk ratios were used to calculate by random effects models. The primary outcome was the proportion of patients with > 5% weight gain. Seventeen studies with 3457 participants were included. For primary outcomes, 1 study with 124 participants showed olanzapine increased the proportion of patients with > 5% weight gain compared with placebo (60% vs. 9%, P < 0.001). Versus active controls (3 studies, 439 participants), no significant difference in the proportion of patients with > 5% weight gain (RR = 1.69, 95%CI: 0.91 to 3.13, I2 = 27%, P = 0.10), with moderate-quality evidence. Olanzapine increased appetite scores compared to both placebo (1 study, 112 participants; MD = 3, 95%CI: 2.3 to 3.7, P < 0.001) and active controls (2 studies, 106 participants; MD = 4.96, 95%CI: 4.61 to 5.30, I2 = 0%, P < 0.01). For mean weight change, olanzapine showed no significant differences versus placebo (2 studies, 164 participants, MD = 2.78kg, 95%CI: - 1.60 to 7.17, I2 = 48%, P = 0.21) or active controls (2 studies, 480 participants, MD = 0.44kg, 95%CI: - 1.04 to 1.91, I2 = 58%, P = 0.56). Olanzapine appears to be a potential option for improving appetite and weight gain in cancer patients. Future trials need to focus on the optimal target dose and use durations of olanzapine. Registered: https://archive.org/details/osf-registrations-kpv4h-v .