Background: Malaria remains a major public health burden in Ethiopia, particularly in rural regions where access to synthetic repellents is limited. Indigenous communities have traditionally used medicinal plants for mosquito protection, yet scientific validation of these practices remains insufficient. Purpose: This study investigated the chemical composition, repellent efficacy, and practical applicability of four Ethiopian medicinal plants, Cymbopogon citratus, Ocimum suave, Azadirachta indica, and Eucalyptus globulus, against Anopheles mosquitoes, comparing their performance to DEET. Findings: Phytochemical analysis revealed citronellal as the most abundant compound (65% total accumulation). Laboratory tests showed C. citratus and O. suave achieved >90% initial repellency, comparable to DEET (97.2%). Field trials in Dire Dawa, Harari, and Somali regions demonstrated 75% and 70% bite reduction over two hours, respectively. Statistical analysis confirmed significant differences among treatments (F (4,95) = 217.48, p < 0.001) with a large effect size (η² = 0.9015). Strong positive correlation was observed between citronellal concentration and efficacy (r = 0.834). Cymbopogon citratus and Ocimum suave are effective, accessible alternatives to synthetic repellents for malaria prevention in rural Ethiopia. Recommendation: These plants should be integrated into community-based malaria control programs, with standardized formulations and further commercialization studies.