BACKGROUND: This study aims to identify major risk factors for diabetic kidney disease (DKD) and examine their causal relationships using meta-analysis and Mendelian randomization. MATERIALS AND METHODS: This study reviewed diabetic nephropathy literature up to September 2024, evaluating quality with NOS, AMSTAR 2, and JBI. It analyzed heterogeneity using the Baujat plot and leave-one-out method, and conducted meta-analysis with fixed- or random-effects models based on I. Publication bias was assessed with a funnel plot and Egger's test. Mendelian randomization using GWAS SNPs explored causal links through IVW, MR-Egger, weighted median, and weighted mode, while pleiotropy and heterogeneity were checked with the MR-Egger intercept and Cochran's Q. RESULTS: Meta-analysis identified several significant risk factors for DKD, including hypertension (relative risk [RR] = 6.33), comorbidities (RR = 4.96), poor glycemic control (RR = 3.27), non-adherence to treatment (RR = 3.30), an unhealthy diet (RR = 5.96), physical inactivity (RR = 5.60), and hyperuricemia (RR = 5.24). MR analysis further confirmed a causal relationship between high carbohydrate intake (odds ratio [OR] = 1.393,  = 0.043) and increased DKD risk, while vegetable consumption (OR = 0.816,  = 0.011) was identified as a protective factor. These findings reinforce the critical role of dietary and lifestyle interventions in DKD prevention. CONCLUSIONS: By integrating meta-analysis with Mendelian randomization, this study provides robust evidence linking modifiable risk factors, particularly dietary habits and lifestyle behaviors, to DKD development. The findings highlight the need for early preventive strategies targeting glycemic control, hypertension, and dietary modifications to mitigate DKD progression.