Background: Despite global malaria control efforts, malaria continues to cause approximately 241–249 million cases and over 600,000 deaths annually. Ivermectin, a broad-spectrum antiparasitic drug with endectocidal activity against mosquitoes feeding on treated hosts, has been proposed as a potential malaria vector-control intervention. Objective: To systematically evaluate the effectiveness of ivermectin in reducing malaria transmission outcomes in adult populations, including malaria incidence, prevalence, mosquito mortality, and safety outcomes. Methods: Following PRISMA 2020 guidelines, we included randomized controlled trials (RCTs) and cluster-RCTs evaluating ivermectin compared with placebo, standard care, or non-ivermectin controls in adult populations. Outcomes included malaria incidence, prevalence, mosquito mortality, and adverse events. Results: Ten randomized trials involving 63,192 participants were included. Community-level analyses showed no significant reduction in malaria prevalence, with very wide confidence intervals reflecting substantial imprecision. Entomological trials demonstrated increased mosquito mortality following ivermectin exposure (RR 1.89; 95% CI 1.26–2.83), although heterogeneity was substantial (I ² > 97%). Across studies, ivermectin was generally well tolerated, with no significant increase in adverse events. Conclusions: Current evidence does not demonstrate consistent reductions in malaria incidence or prevalence with ivermectin administration, although laboratory and experimental studies suggest mosquitocidal effects. Further large, well-designed cluster-randomized trials are required to determine whether ivermectin can contribute to malaria control strategies.