Avocado (Persea americana Mill.) fruit and oil are traditionally used for their antioxidant, anti-inflammatory and anti-aging properties. We investigated chemical variability between two avocado cultivars (Duke and Fuerte) in relation to their antioxidant and anti-inflammatory activities. Duke cultivar showed higher β-carotene and α-tocopherol content but significantly lower lipid content (36% dry weight) compared to Fuerte (52% dry weight). The ethanolic extract of Duke cultivar showed good antioxidant properties in 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay with IC 50 at 27.21 μg/ml, while that of Fuerte showed weak activity. Meanwhile, in rat paw edema anti-inflammatory model, Duke oil (15 mg/kg) was slightly more effective in reducing inflammation by 41.12% after 1 h compared to Fuerte oil (15 mg/kg). However, after 4 h, both oils showed comparable inhibition of edema by 35.39% and 34.14% (15 mg/kg). The study underscores that variability in chemical composition of different avocado cultivars could affect biological activities attributed to the fruit and its oil.