Piper guineese (Piperaceae) seed are locally used after childbirth to facilitate the removal of clotted blood. The present study evaluated the in vitro antioxidants, membrane stability, thrombolytic and erythrocytes protective activities of piper guineense (Ashanti) seed extract. 100 g of Piper guineese seed was pulverized and dissolved in 500 ml of distilled water for 24 hours. The extract obtained was concentrated using a rotary evaporator. The IC₅₀ for 2,2-diphenyl-1-picrylhydrazyl scavenging activities of the seed and utylated hydroxytoluene (BHT) were 2.82 and 1.39 mg/ml. Furthermore, IC₅₀ for total antioxidant capacity and hydrogen peroxide scavenging activities of the seed and BHT were 2.63, 1.28 mg/ml and 2.13 and 1.61 mg/ml respectively. The IC₅₀ values for hydroxyl radical scavenging activities and nitric oxide reducing power were 3.145, 1.75 mg/ml and 7.37, 2.32 mg/ml respectively. However, no significant difference were found in ferric ion reducing properties of the extract and BHT with IC₅₀ values of 2.06 and 2.53 mg/ml respectively. The extract expresses 38.94±4.89% erythrocyte lysis activities at a concentration of 100 µg/ml. Thrombolytic activity of the seed (10.08%) was comparable to BHT (11.43%) and lower compared with acetylsalicylic acid (94.05%) and streptokinase (67.10%). The extract significantly (p<0.05) inhibited (29.58%) hypotonic solution-induced erythrocyte membrane lysis when compared to BHT (38.859%) and NaCl control (100%) respectively. The highest erythrocytes protection of the extract was 36.24% compared with Phosphate Buffer Saline (66.94%) and BHT (47.76%). The study demonstrated the in vitro antioxidant properties and erythrocyte protective activities of aqueous extracts of Piper guineese seeds.