Background: Leaf extracts of Pterocarpus santalinoides are used in ethno-medicine for the treatment of liver diseases, and studies had validated its efficacy. Aim: This study evaluated the blood cellular, serum biochemical, and organosomatic alterations associated with sub-acute oral administration of Pterocarpus santalinoides methanolic leaf extract (PSMLE) to albino rats. Methods: To be used for the study, 25 female rats were randomly assigned into four groups (1–4) of five each. Group 1 rats (untreated control) were given distilled water placebo, while Groups 2, 3, and 4 were treated orally with 50, 250, and 500mg/kg PSMLE, respectively. Treatment was done daily for 28 days after which blood samples were collected for hematology and blood biochemistry. The rats were afterwards humanely sacrificed, and the liver, kidneys, heart, and spleen were eviscerated and weighed. Results: Serum total protein levels of Group 2 and Group 3 rats were significantly (p<0.05) higher than that of Groups 1 and 4, while serum globulin levels of Group 2 were significantly higher (p<0.05) than that of Groups 1 and 4. All other serum biochemical and all hematological parameters and the relative liver, kidney, spleen, and heart weights did not significantly (p>0.05) vary among the groups. Mean body weights of Group 3 rats were significantly (p<0.05) higher than that of Groups 1 and 2 on Day 28. Conclusion: Sub-acute administration of PSMLE to rats led to no significant hematological, serum biochemical, and organosomatic alterations, except for significantly higher serum total proteins and globulins and higher body weights.