In the current study, anti-osteoporotic activities of crocin were evaluated in a rat model of metabolic syndrome-induced osteoporosis. Metabolic syndrome was confirmed by increased body weight gain, increased fasting blood glucose, hyperinsulinemia, elevated mean arterial blood pressure, and increased serum triglycerides level. Crocin (5 or 10 mg/kg) protected against histological and architectural alteration in bone tissues. Further, it ameliorated the decline in the bone formation markers serum alkaline phosphatase activity and osteocalcin level and inhibited the rise in the bone resorption markers serum tartrate-resistant acid phosphatase and collagen cross-linking carboxyterminal telopeptide, type I. Crocin anti-inflammatory properties were confirmed by a significant decline in serum interleukin-6 and tumor necrosis factor-α. Crocin mitigated oxidative stress in femur distal epiphysis tissues. Mechanically, crocin enhanced both the longitudinal and perpendicular forces of femurs. The current data highlight a protective activity that can be attributed, at least partly, to its anti-inflammatory and antioxidant activities. PRACTICAL APPLICATIONS: Metabolic syndrome is a serious health problem. Its prevalence is present in approximately 25% of all adults. Complications of metabolic syndrome include osteoporosis. This poses high risk of fractures and represents a heavy health, social, and economic burden. The current study highlights the antiosteoporotic activities of crocin in an experimental model of osteoporosis. Thus, crocin and/or other structurally related carotenoids can be lead compounds for synthesizing more potent and bioavailable molecules. These are expected to be devoid of the hazardous adverse effects of the currently available medicaments.