The current experiment was intended to investigate the hepatoprotective, immunostimulant activity, behavioural and anxiety responses of mice supplemented with Eruca sativa aqueous extract (ESAE) at a dose of 1% in drinking water in healthy and thioacetamide (TAA) intoxicated male mice. Eighty male albino mice were divided into four treatments of 20 mice each, with two replicates. The T1 considered as control group, T2 was the TAA intoxicated group, T3 was supplemented with ESAE only in drinking water for 3 weeks, and T4 supplemented with both ESAE for 3 weeks and TAA in the last 3 days in drinking water. The effect of ESAEwas assessed by estimation of erythrogram, leukogram, platelet count, N/L ratio, total protein, albumin, globulin, and A/G ratio, and by evaluating the activity of liver enzymes such as aspartate transaminase (AST) and alanine transaminase (ALT) as well as the behavioural responses and anxiety of mice were also recorded. ESAE administration markedly prevents the elevation of plasma liver enzymes after oral administration of TAA. The mice supplemented with ESAE (T3) had higher mean values of total protein, globulin, with lower neutrophils count and A/G ratio compared to the control group (T1) and TAA intoxicated mice (T2), indicating that ESAE has immunostimulant and hepatoprotective activity. The mice supplemented with ESAE (T3) groomed, scratched, and sniffed significantly more than mice of T2, with significantly less resting and sleeping. Regarding the elevated plus maze results; when comparing mice of T1 and T2 with other treatments, the mice of T3 and T4 showed a huge (P<0.05) decline in the quantity of closed arms entries, with a relating increase in the quantity of open arms entries. It is concluded that a daily oral dose of 1% ESAE improves mouse activity, reduces anxiety, and has immunostimulant and hepatoprotective activity.