Objective To review the relationship between CDKAL1 gene rs7756992 A>G polymorphism and the susceptibility to type 2 diabetes mellitus (T2DM). Methods Electronic databases including China National Knowledge Infrastructure (CNKI), Wanfang database, EMBASE, PubMed and ScienceDirect were searched. Case-control studies on the relationship between CDKAL1 gene rs7756992 A>G polymorphism and the susceptibility to T2DM were selected based on the inclusion and exclusion criteria of original document. The pooled odds ratio (OR) with 95% confidence interval (CI) of the relationship between CDKAL1 gene rs7756992 polymorphism and the susceptibility to T2DM were calculated using different genetic models. Subgroup analysis based on the population of different ethnicities and sensitivity analysis were performed. Results Fourteen studies including 24 315 participants in T2DM group and 35 132 in control group were identified in this analysis. Meta analysis showed that CDKAL1 gene rs7756992 A>G polymorphism was associated with the susceptibility to T2DM under different genetic models (allele [G vs A]: OR=1.171, 95%CI: 1.122-1.223, P<0.001; co-dominant [GG vs AA]: OR=1.380, 95%CI: 1.258-1.515, P<0.001; co-dominant [AG vs AA]: OR=1.131, 95%CI: 1.089-1.176, P<0.001; dominant [AG+GG vs AA]: OR=1.168, 95%CI: 1.101-1.240, P<0.001; recessive [GG vs AA+AG]: OR=1.343, 95%CI: 1.282-1.405, P<0.001). Results of subgroup analysis showed that CDKAL1 gene rs7756992 G allele significantly increased the risk of T2DM in both Asian and Caucasian populations (P<0.05), but there was no significant difference in African population. Conclusion The mutations of A>G allele of rs7756992 locus in CDKAL1 gene may be a risk factor for T2DM in Asian and Caucasian population.