Background <p>Vascular endothelial growth factor (VEGF) inhibitors are associated with a high incidence of proteinuria. In patients with diabetes, increased proteinuria is closely associated with decreased renal function; however, the impact of increased proteinuria on renal function in patients with cancer and diabetes mellitus undergoing VEGF inhibitor therapy remains unknown.</p> Methods <p>The incidence of proteinuria and renal function in patients with cancer and a history of diabetes who were treated with VEGF inhibitors at the National Cancer Center Hospital East between January 2018 and December 2019 was retrospectively investigated.</p> Results <p>Among the 49 patients included, 21 (43%) developed proteinuria ≥ 3 + after VEGF inhibitor treatment. In all patients, a decreasing trend in the estimated glomerular filtration rate (eGFR) was observed beginning 2 years after treatment initiation. The decrease in eGFR from baseline was − 6.6% at 1 year, -11% at 2 years, and − 13% at 4 years. Patients who developed proteinuria ≤ 2 + showed no significant decrease in eGFR from baseline to either the end of treatment (<i>p</i> = 0.91) or the latest value during the observation period (<i>p</i> = 0.64). Similarly, no significant decrease in eGFR was observed in those with proteinuria ≥ 3+ (end of treatment, <i>p</i> = 0.91; latest value during the observation period, <i>p</i> = 0.18).</p> Conclusions <p>In patients with cancer and diabetes mellitus, increased proteinuria after VEGF inhibitor therapy suggested that it was not associated with a significant decline in renal function.</p>