Abstract Background Infection is the most feared complication of a penile prosthesis. Diabetes mellitus (DM) is widely known to increase the risk of several infections, but its role in the penile prosthesis is still controversial. This systematic review aims to show the contemporary scenario of penile prosthesis infection and present a meta-analysis about DM contribution to penile prosthesis infection. Methods The review was performed with no language or time limitation, including ten databases. The included articles were about the male population who received a penile prosthesis with no model restriction, with a minimum follow up of 1 year, and outcomes adequately reported. Results The mean infection incidence of penile prosthesis ranged from 0.33 to 11.4%. In early 2000, the general incidence of infection was 3 to 5%, then, the introduction of coated materials decreased it to 0.3 to 2.7%. The meta-analysis showed that diabetes mellitus is related to an increased risk of penile prosthesis infection with an odds ratio of 1.53 (95% CI 1.15–2.04). Conclusions Penile prosthesis infection decreased in the last decades but remains a significant cause of reoperation, and it is related to lower prosthesis survival. Meta-analysis concludes that diabetes mellitus is related to a higher risk of penile prosthesis infection.