Although previous studies suggested the protective effect of zinc for type-2 diabetes (T2D), the unitary causal effect remains inconclusive. We investigated the causal effect of zinc as a single intervention on glycemic control for T2D, using a systematic review of RCTs and two-sample Mendelian randomization (MR). Four primary outcomes were identified: fasting blood glucose/fasting glucose, HbA1c, HOMA-IR, and serum insulin/fasting insulin level. In the systematic review, four databases were searched from the establishment to June 2021. Studies, in which participants had T2D and intervention did not comprise another co-supplement, were included. Results were synthesized through the random-effects meta-analysis. In the two-sample MR, we used random allocation of single nucleotide polymorphisms (SNPs), strongly related to zinc supplements, to infer the relationship causally, but not specified T2D. SNPs were from MR-base. In the systematic review and meta-analysis, 14 trials were included with a total of 897 participants. The zinc supplement led to a significant reduction in the post-trial mean of fasting blood glucose (mean difference (MD): -26.52 mg/dL, 95%CI: -35.13, -17.91), HbA1c (MD: -0.52%, 95%CI: -0.90, -0.13), and HOMA-IR (MD: -1.65, 95%CI: -2.62, -0.68), compared to the control group. In the two-sample MR, zinc supplement with 2 SNPs reduced the fasting glucose (inverse-variance weighted coefficient: -2.04 mmol/L, 95%CI: -3.26, -0.83). From systematic review and two-sample MR analyses, zinc supplementation alone may causally improve glycemic control among T2D patients. The findings are limited by power from the small number of studies and SNPs included in the systematic review and two-sample MR analysis respectively.