The present study investigates effect of Sida rhomboidea ROXB. (S. rhomboidea ROXB., SR) on high fat diet (HFD) induced insulin resistance in C57BL/6J mice and the results obtained have been compared with mice fed with rosiglitazone (ROS). Changes in bodyweight, food intake, fasting blood glucose, plasma insulin, plasma and hepatic triglyceride (TG), total cholesterol (TC) and free fatty acids (FFAs) have been investigated in various experimental groups. It was observed that feeding of SR extract to HFD fed mice (HFD+SR) reduced bodyweight (p < 0.05), food intake (p < 0.05) and feed efficiency ratio (p < 0.05). Plasma and hepatic TC, TG and FFA were also significantly lowered (p < 0.05) in HFD+SR groups. Efficient clearance of glucose in intraperitoneal glucose tolerance test (IPGTT), lowered area under curve (AUC glucose) values, low plasma insulin and fasting insulin resistance index (FIRI) coupled with higher K ITT values were observed in HFD+SR groups. These findings were further justified by significant reduction of adipocyte diameter (p < 0.05) and surface area (p < 0.05) in HFD+SR groups. This study is a first scientific report on protective role of S. rhomboidea ROXB. extract against HFD induced insulin resistance in C57BL/6J mice and strengthens the folklore claim of use of SR leaves as alternative medicine against diabetes and obesity.