Xylopia aethiopica (Annonaceae) is medicinally important in the treatment of a wide range of diseases. In Nigeria, Xylopia aethiopica whole seed are locally used in the treatment of constipation. They are used as a tonic in tea and beverages, and after pregnancy delivery to facilitate the removal of clothing blood in the system. This study evaluated the plasma oxidation properties and in vitro antioxidant activities of Xylopia aethiopica whole seed and pod. 50 g Each of seed, pod and whole seed of Xylopia aethiopica were pulverized and dissolved separately in 250 ml of distilled water for 24 hours. The obtained extracts were concentrated using a rotary evaporator. The 2,2-diphenyl-1-picrylhydrazyl scavenging activities of the seed (IC₅₀ = 0.19±0.03 mg/ml) and pod (IC₅₀ = 0.24±0.02 mg/ml) extracts were similar with butylated hydroxytoluene (IC₅₀ = 0.17±0.04 mg/ml) and ascorbic acid (IC₅₀ = 0.13±0.05 mg/ml). Furthermore, total antioxidant capacity and nitric oxide reducing power of the seed, pod and whole seed were similar with no significant difference (p>0.05) when compared with butylated hydroxytoluene. However, the seed (IC₅₀ = 0.89±0.09 mg/ml), pod (IC₅₀ = 0.35±0.03mg/ml) and whole seed (IC₅₀ = 0.32±0.03 mg/ml) expressed significantly (p<0.05) lowered hydrogen peroxide decomposing activity when compared with butylated hydroxytoluene (IC₅₀ = 0.15±0.00 mg/ml) and ascorbic acid (IC₅₀ = 0.15±0.01 mg/ml). The extract expressed no erythrocyte lysis activities at a concentration range of 6.25 – 100 µg/ml. Protective effects of the extract of Xylopia aethiopica were concentration dependent, with lower doses (6.25 – 25 µg/ml) having more protective effects against accumulation of CuSO₄-induced conjugated dienes in plasma. Similarly, the seed, pod and whole seed demonstrated significant (p<0.05) thrombolytic activity compared with normal control but not significantly compared with streptokinase. The extracts significantly (p<0.05) inhibited hypotonic solution-induced erythrocyte membrane lysis when compared to NaCl control and reference drug acetylsalicylic acid respectively. The present study demonstrated the protective nature of Xylopia aethiopica L. seed, pod and whole seed extracts against the accumulation of conjugate dienes, thrombolytic activities and membrane stability effects. Xylopia aethiopica L. seeds are recommended for consideration as a significant natural antioxidant source.