This research aimed to assess the effect methanol extract from Padina astraulis (Hauk , 1887) on biochemical response and digestive enzyme activities in grey mullet, Mugil cephalus (Linnaeus, 1758). A control diet without and three other empirical regimens were prepared with the addition of of P.astraulis extract (PE diet) at the incorporation levels of 5, 10 and 15 g kg-1 diet, respectively. Three hundred sixty grey mullet with an introductory mean weight of 0.82 g were randomly dispersed into twelve fish tanks and fed twice a day (09:00 and 17:00) for 60 days. After 60 days of the feeding trial, no significantly different was noticed in terms of survival rate between control and the groups supplemented with PE (p>0.05). Dietary PE significantly increased serum total protein, globulin levels and amylase, lipase and protease enzyme activities in treated fish (p<0.05). Moreover, there was considerable decline (p<0.05) in cholesterol, glucose and triglyceride levels in those fish which received PE diet over the control. The current research illustrates the appropriateness of P. astraulis extract as a novel dietary additive in grey mullet diet for improving metabolism of lipid and carbohydrate and enhancing digestive enzyme activities in grey mullet.