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Objectives This systematic review aims to evaluate the efficacy of neuroprotective therapies in improving best-corrected visual acuity (BCVA) in retinitis pigmentosa (RP). Secondary outcomes investigated included electroretinogram measures (ERGs), adverse events and other relevant ophthalmological outcomes.Methods and analysis A systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered on PROSPERO. MEDLINE, EMBASE, ClinicalTrials.gov and the Cochrane Library were searched without date restrictions. Randomised controlled trials comparing neuroprotective interventions with any relevant comparator in typical RP and reporting BCVA outcomes were included. Risk of bias was assessed using ROB2 and certainty of evidence graded using Grading of Recommendations Assessment, Development and Evaluation (GRADE). Due to heterogeneity in interventions and outcome reporting, narrative synthesis was undertaken.Results 10 trials involving 1364 participants were included. Interventions included antioxidants, gamma-aminobutyric acid (GABA) modulators, mechanical neurostimulation and omega-3 fatty acids. Across studies, no neuroprotective therapy demonstrated a clinically or statistically significant improvement in BCVA compared with control, with the exception of Lycium barbarum, which was associated with modest BCVA improvement in a single phase II trial with a very low GRADE certainty of evidence. Vitamin A, docosahexaenoic acid and lutein were associated with changes on secondary outcomes, such as ERG amplitudes, in phase III trials, though findings were from secondary analyses. Overall certainty of evidence was moderate to very low.Conclusions Current evidence does not support the use of neuroprotective therapies to preserve visual acuity in RP. While some interventions show promise, including in secondary functional measures, robust conclusions are limited by small sample sizes and methodological heterogeneity. Larger, standardised trials are required to validate the role of neuroprotection in RP.