The association between smoking and psychopathology and extrapyramidal side effects (EPSE) in schizophrenia has been controversial. This systematic review and meta-analysis compared psychopathology and EPSE between smoking and non-smoking schizophrenia patients. The PubMed, EMBASE, PsycINFO, Cochrane Library, and Web of Science databases were independently and systematically searched by two researchers to identify relevant articles. Standardized mean differences (SMDs) and their 95% confidence intervals (CI) were calculated with random effect models. Subgroup and meta-regression analyses were performed to explore sources of heterogeneity. The systematic review and meta-analysis included 29 studies that compared psychotic, depressive and anxiety symptoms and EPSE between smoking (n = 3591) and non-smoking schizophrenia patients (n = 2980). Smoking patients had significantly more severe positive symptoms (24 studies; SMD = 0.33, 95% CI: 0.16 to 0.50, P < 0.001), but less severe EPSE (7 studies; SMD = −0.20, 95% CI: −0.38 to −0.02, P = 0. 03). No significant group differences in negative, depressive and anxiety symptoms were found. In conclusion, this systematic review and meta-analysis found that smoking schizophrenia patients had more severe positive symptoms but less severe EPSE than non-smoking patients.