Study objective. The objective of this research was to evaluate the efficacy of alendronate, hops extract and their combination on bone tissue quality, oxidative stress damage, organ histomorphology, changes in metabolism, hematological parameters, and biochemical parameters in a rat model of osteoporosis. Study design. The study was designed as a randomized controlled experiment on the rat ovariectomy model of osteoporosis. Materials and methods. The study was performed on 6 months old female Wistar rats. A sham operation was done on 10 animals, and bilateral ovariectomy on 60 animals. Ovariectomized animals were divided into 6 groups from which one was not treated while the rest was treated with a low dose of alendronate, high dose of alendronate, hops extract, or a combination of low/high dose of alendronate and hops extract. Analyses of hematological and biochemical blood parameters, bone tissue quality (micro CT, western blot of serum bone turnover markers), organ histomorphology, oxidative stress markers, and MALDI-TOF-MS analysis of adipose tissue and liver were performed. Results. Administration of a high dose of alendronate, hop extract, or combination of low dose alendronate and hop extract significantly improved bone quality in ovariectomized animals. The levels of bone remodeling indicators did not differ significantly, except for the increased level of P1NP in the group that received a high dose of alendronate. Indicators of oxidative damage did not differ significantly in the examined groups. The tested substances did not cause accumulation of connective tissue in the liver, morphological changes in the uteri of ovariectomized animals, or proliferation of endometrial cells. Adipocytes were smaller in the group that received only hop extract. The tested substances affected the hematological and biochemical characteristics of the animals to a certain extent, but no adverse effect was observed. Serum cholesterol was elevated in the treated with hops extract, and liver triglyceride levels were decreased in all ovariectomized groups compared to the untreated ovariectomized group. MALDI-TOF-MS analysis indicated changes in the metabolism of the liver and perigonadal adipose tissue in all experimental groups. Conclusion. Therapy with a high dose of alendronate, hops extract or a combination of a low dose of alendronate and hop extract favorably affects bone quality in ovariectomized animals without significant adverse effects.