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Background and Aim:Osteoporosis is one of the most common bone diseases that is caused by an imbalance between the activity of osteoblasts and osteoclasts. Osteoprotegerin (OPG) plays an active role in inhibiting osteoclasts by binding to the receptor activatorofnuclearfactor kappa-B ligand (RANKL). The balance in the OPG/RANKL ratio is important in bone remodeling. The current study investigated and compared the effects of mumie extract and chemical drugs on cell proliferation, expression of OPG and RANKL in MG63 cells.Materials and Methods:The effects of 100, 200 and 300 μg/mlof mumie extract on cell proliferation, expression of OPG and RANKL in MG63 cells were investigated in experimental groups, positive and negative control groups. Data were analyzed byANOVA test.Results: Significant increases were observed in the proliferation of MG63 cells after exposure to 100 and 200 μg/mlconcentrations of mumie extract. 200 μg/mlconcentration of the extract significantly decreased the expression of RANKL and increased theexpression of OPG. It also increased OPG/RANKL ratio significantly in the experimental groups, compared to those in the negative control groups. Although the effects of 100 μg/mland 200 μg/mlconcentrations were similar to each other, they showed no significant effects on the variables. 300 μg/ml concentration of the extract showed a reverse and insignificant effect.Conclusion:200 μg/ml concentration of mumie extract had a significant effect on the expression of two important factors in bone remodeling.Therefore, individuals susceptible to osteoporosis can use mumie extract as an alternative to chemical drugs.