AbstractThis study aimed to evaluate the effect of saffron, crocin, and safranal on serum levels of oxidants and antioxidants in diabetic rats. The authors searched the databases with standard keywords until June 8, 2021. The random‐effects model was used to pool standardized mean differences (SMD) with 95% confidence intervals to assess the effects of saffron and its active component. To investigate heterogeneity, subgroup analysis and meta‐regression were utilized. Begg and Egger's tests were used to measure publication bias. Our results showed that saffron, crocin, and safranal were able to significantly reduce the serum levels of oxidants with strong efficacy so that saffron had the highest effectiveness on serum malondialdehyde (SMD, −2.84 (μmol/L) [95% confidence interval (CI), −4.32 to −1.36];p< .001,I2= 83.5%). In addition, saffron and its effective compounds were highly effective by increasing the serum level of antioxidants. In addition, saffron and its effective compounds were able to significantly increase the serum level of antioxidants with strong efficacy, while saffron had the highest effect on the serum level of total antioxidant capacity (SMD, 3.90 (μmol/L) [95% CI, 0.78–7.03];p= .014,I2= 86.9%). The findings of this study show that treatment with saffron, crocin, and safranal by strengthening the antioxidant defense system and modulating oxidative stress shows antidiabetic effects in the diabetic model of rats, also these findings support the potential effect of saffron and its effective compounds for the management of diabetes and its complications. However, more human studies are needed.