BACKGROUND: Urethral stricture disease is a common problem amongst men in Western countries often leading to a decreased quality of life. Current endoscopic treatment procedure shows an unsatisfying stricture recurrence rate which could be improved by addition of local therapies. OBJECTIVES: To provide an overview of both preclinical and clinical studies in order to investigate current level of evidence on the addition of local therapy to improve urethral stricture recurrence rates after endoscopic procedures. METHODS: We performed a literature search in December 2020 and August 2021 using Cochrane, Embase, PubMed, Scopus and Web of Science and identified articles through combinations of search terms for 'urethral stricture disease', 'stricture formation' and 'local interventions'. We used the SYRCLE, RoB-2 and ROBINS-I tools to assess risk of bias across included studies. We did not perform a meta-analysis due to methodological differences between studies. RESULTS: We included 32 articles in the qualitative analysis, 20 of which were preclinical studies and 12 clinical studies. Regarding preclinical articles using an animal model, nearly all interventions showed to have a positive effect on either urethral fibrosis, urethral stricture formation and/or fibrotic protein expression levels. Here, immunosuppressants and chemotherapeutics seemed most promising for possible clinical purposes. Regarding clinical studies, mitomycin-C and hyaluronic acid and carboxymethylcellulose showed positive effects on urethral stricture recurrence rates with low to intermediate risk of bias across studies. However, the positive clinical effects of mitomycin-C and steroids seemed to decrease in studies with a longer follow-up time. CONCLUSION: Although local adjuvant use of mitomycin-C or hyaluronic acid and carboxymethylcellulose may carry clinical potential to improve urethral structure recurrence rates after endoscopic procedures, we believe that a large, well-designed RCT with a yearlong follow-up time is necessary to identify the true clinical value.