Supplementation with cannabidiol (CBD) may expedite recovery when consumed after exercise. The purpose of this study was to determine if supplementation with CBD reduces inflammation and enhances performance following strenuous eccentric exercise in collegiate athletes. Twenty-four well-trained females (age = 21.2 ± 1.8 years, height = 166.4 ± 8 cm, weight = 64.9 ± 9.1 kg) completed 100 repetitions of unilateral eccentric leg extension to induce muscle damage. In this crossover design, participants were randomized to receive 5 mg/kg of CBD in pill form or a placebo 2 h prior to, immediately following, and 10 h following muscle damage. Blood was collected, and performance and fatigue were measured prior to, and 4 h, 24 h, and 48 h following the muscle damage. Approximately 28 days separated treatment administration to control for the menstrual cycle. No significant differences were observed between the treatments for inflammation, muscle damage, or subjective fatigue. Peak torque at 60°/s (p = 0.001) and peak isometric torque (p = 0.02) were significantly lower 24 h following muscle damage, but no difference in performance was observed between treatments at any timepoint. Cannabidiol supplementation was unable to reduce fatigue, limit inflammation, or restore performance in well-trained female athletes.