Osteoporosis, a systemic skeletal disease characterized by a decrease in bone mass and deterioration of bone structure leading to an increased risk of fragility fractures, represents one of the major health problems worldwide. Currently, there are numerous pharmacological products used for the treatment of osteoporosis. Anti-resorptive drugs include bisphosphonates, hormone therapy, selective estrogen-receptor modulators, calcitonin, denosumab, calcium and vitamin D supplementation. Anabolic drugs such as teriparatide, strontium ranelate, romosozumab have recently become available based on advanced clinical trials. In recent years, combination therapy of anabolic and anti-resorptive agents is expected to be ideal anti-osteoporosis option. The adverse side effects caused by the long-term administration of pharmacological drugs have prompted researchers to study natural therapeutic compounds to find an alternative and effective way for osteoporosis treatment. Natural compounds including phytoestrogens with estrogenic effects (e.g. genistein, daidzein, icariin, dioscin, Ginkgo biloba), antioxidant and anti-inflammatory agents (e.g. acteoside, curcumin, resveratrol, Camellia sinensis), treatments that exert their effects by multiple actions (e.g. kinsenoside, berberine, Olea europaea, Prunus domestica, Allium cepa) could provide a safer alternative to primary pharmacological strategies. In this review, both pharmacological agents and natural compounds as available treatments for osteoporosis are characterized. In addition, possible mechanisms of action of all aforementioned treatments associated with bone remodelling, osteoclastogenesis, osteoblastogenesis, bone cell activity, death, and oxidative stress are presented. Nevertheless, more high-quality clinical studies with natural compounds are needed to provide greater evidence of the beneficial and safer antiosteoporotic application for the candidate.