The Cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like (CDKAL1) gene rs7756992 A/G polymorphism has been suggested to be associated with type 2 diabetes mellitus (T2DM), but the individual studies results are still controversial. To explore the association of CDKAL1 gene rs7756992 A/G polymorphism with T2DM, a meta-analysis involving 62,567 subjects from 21 separate studies was conducted. In the whole population, a significant association was found between CDKAL1 gene rs7756992 A/G polymorphism and T2DM under allelic (OR: 1.180, 95% CI: 1.130-1.230, P = 1.60 × 10⁻¹⁴), recessive (OR: 1.510, 95% CI: 1.380-1.660, P = 8.41 × 10⁻¹⁸), dominant (OR: 1.175, 95% CI: 1.109-1.246, P = 6.30 × 10⁻⁸), homozygous (OR: 1.400, 95% CI: 1.282-1.530, P = 8.02 × 10⁻¹⁴), and heterozygous genetic models (OR: 1.101, 95% CI: 1.040-1.166, P = 0.001). CDKAL1 gene rs7756992 A/G polymorphism was significantly associated with T2DM. The person with G allele of CDKAL1 gene rs7756992 A/G polymorphism might be predisposed to T2DM.