The research and development of pharmaceutical intervention is insufficient for the frail elderly, especially in preclinical stage for the frail individuals with osteoporosis. Garlic exerts an anti-osteoporotic effect and its vital component allicin could protect organisms against aging. The present study aimed to investigate the effect of long-term intragastric administration of allicin (low-dose of 4 mg·kg-1·d-1; middle-dose of 8 mg·kg-1·d-1; high-dose of 16 mg·kg-1·d-1) on frailty with osteoporosis in aging male Fischer 344 rats. Frailty was assessed with a 27-item frailty index (FI) based on quantifying health-related deficits in adult male rats varied from 13 to 21 months, and in control rats from 6 months to 9 months. Osteoporosis was appraised by bone mineral density (BMD) detected by Dual-energy X-ray Absorptiometry (DXA), biomechanical properties measured by a three-point bending test and bone metabolic analysis using ELISA. Allicin could attenuate FI scores by reducing accumulation of health deficits in aging male Fischer 344 rats. Meanwhile, allicin could protect against senile osteoporosis, and the underlying mechanism may involve in increasing low bone turnover through elevation of both bone formation and bone resorption, and subsequently lead to increase of BMD, contributing to reversing deleterious bone biomechanical features associated with aging. The present study reveals firstly that long-term oral administration with allicin attenuated frailty with osteoporosis during the process of aging which provides a preclinical evidence for intervention of frailty.