Chronic use of glucocorticoids is one of the most common causes of osteoporosis. Triterpenes have a positive effect on bone metabolism, which encourages research into the anti-resorptive properties of these natural compounds. In this study, the antiresorptive effect of the semisynthetic compound 3b,6b,16b-tripropionyloxylup-20(29)-ene (CL-P2), obtained from the natural lupane-type triterpene 3b,6b,16b-trihydroxylup-20(29)-ene (CL-1) isolated from Combretum leprosum Mart., was investigated in a glucocorticoid-induced osteoporosis (GIO) model in rats. GIO was induced by dexamethasone (7 mg/kg, im; 1 /week, 65 days). On the 36th day, treatment was started (gavage) with CL-P2 (0.01 or 0.1 mg/kg; 30 days). After this time interval, the rats were euthanized and the femurs and lumbar vertebrae were collected for analysis by microcomputed tomography (micro-CT), quantity and type of collagen (Picrosirius Red), micro-Raman spectrometry, and histomorphometric analysis using hematoxylin and eosin (H&E) staining. The organs were collected for toxicity analysis (HE). CL-P2 increased trabecular volume, number of trabeculae and bone mineral density as evidenced by micro-CT analysis in the third lumbar vertebra (L3), as well as the amount of total collagen and type I collagen in L2. In the analysis of the femurs, CL-P2 promoted an increase in the number of osteoblasts and osteocytes and a reduction in the number of osteoclasts, as well as change in the mineral composition of these bones, suggested by the increase in the carbonate-to-phosphate ratio (CTPR) identified by micro-Raman spectrometry. Histopathological analysis of the organs revealed the pre-clinical safety of CL-P2. CL-P2 had bone-protective benefits and may be a biotechnologically viable product as a supplemental therapy for GIO.