Objective <p>According to existing epidemiological evidence, whether proton therapy is more efficacious and safe than photon therapy in the treatment of craniopharyngioma (CP) remains controversial. This study aimed to evaluate whether proton therapy exhibits better efficacy and safety in terms of survival outcomes and toxic effects than photon therapy.</p> Methods <p>An extensive search of pertinent articles published between 1990 and February 2025 was performed in the following four databases: PubMed, Web of Science, Embase, and the Cochrane Library. Original studies investigating the efficacy and safety of proton or photon therapy in patients with CP were included. This meta-analysis is reported following the PRISMA reporting guidelines, and data were pooled using a random effects model.</p> Results <p>A total of 43 studies on 2784 patients were included in the meta-analysis. The pooled analysis favored proton therapy over photon therapy in terms of 3-year progression-free survival, 5-year progression-free survival, 5-year overall survival, 3-year local control and 5-year local control but not 3-year overall survival. In the safety analysis, compared with photon therapy, proton therapy was associated with reduced probabilities of visual, neurological, cognitive, and other miscellaneous toxicities, whereas the opposite trend was observed for endocrine toxicity. Subgroup analysis indicated that conventional radiation therapy had superior survival outcomes than stereotactic radiosurgery.</p> Conclusions <p>Compared with photon therapy, proton therapy may be associated with improved survival outcomes and reduced incidence of toxic effects in CP patients. Conventional radiation therapy appears to be more effective than stereotactic radiosurgery.</p>