The present trial conducted to examine the impact of dietary red seaweeds, Sargassum dentifolium polysaccharides supplementation on growth induces, hematological and histological indicators of the hybrid red tilapia Oreochromis mossambicus × Oreochromis niloticus fingerlings. A total of 240 hybrid red tilapia fingerlings with an average body weight of 7.50 ± 0.01 g were divided into four experimental treatments (three replicates each). Four identical isonitrogenous isoenergetic diets except the variation of polysaccharide (SP) levels were formulated. The basal experimental diet (control diet) had no seaweed polysaccharide added (SP0). Diets 2–4 (SP1; SP2 and SP3) was formulated to contained seaweed polysaccharide at levels of 10, 20, and 30 g/kg diet, respectively. Growth performance and feed utilization efficiency of hybrid Red tilapia were significantly (P ≤ 0.05) higher in all treatments receiving SP supplemented-diets than the control diet. The red blood cells (RBCs), hemoglobin (Hb) and hematocrit (Hct, %) values differed significantly (P ≤ 0.05) between the control and fish fed various SP supplemented diets. Considering the dietary SP supplementation, a clear higher trend values of RBC was observed with increasing dietary SP inclusion. Lipase activity recorded the highest values with the fish fed diet supplemented with SP at a level of 20 g/kg-1 associated with the lower significant values amylase activity compared to other treatments. Dietary SP supplementation had no effect on total plasma protein, albumin and globulin levels. Fish fed SP2 diet had an increase in GOT, triglycerides. Fish fed SP3 recorded the lowest value of total cholesterol and LDL when compared to other diets. No abnormal or histological changes were detected in sections of liver, stomach and intestine of red tilapia fed different dietary supplemented with SP levels. The findings of current trial revealed that hybrid Red tilapia fed diets containing red seaweeds, polysaccharides for 12 weeks had enhanced performance, feed conversion ratio and hematological indices.