Osteosarcoma has a poor prognosis and survival rate due to inadequate chemotherapy, high recurrence ability, high metastasis potential, and almost no radiotherapy being applied. One of the strategies to solve these problems is to develop the pharmacologically active plant metabolite, amygdalin, in combination therapeutic systems. In this project, the antiproliferative effects of amygdalin alone and in binary or ternary combinations with some anticancer drugs (cisplatin, 5-fluorouracil, oxaliplatin, and camptothecin), antiparasitic drugs (metronidazole and miltefosine), and an antigout drug (colchicine) were examined using human bone osteosarcoma cell lines (MG-63 and Saos2), the chondrosarcoma cell line (SW1353), and the normal human cell line (FL). Known half-maximal inhibitory concentration values of the drugs were taken into consideration, and the recommended combination ratios were used in the Chou-Talalay method. The strong synergistic effect commonly seen in the combination of amygdalin with miltefosine, metronidazole, camptothecin, colchicine, oxaliplatin, 5-fluorouracil, and cisplatin dual drug indicates that these combinations can be used in cancer treatment. The synergistic effect caused by amygdalin decreases toxicity by increasing drug yield. However, amygdalin antagonism seen in several combinations may prevent these pairs from being used together. In combination with antagonistic effects, it may be preferable to use amygdalin alone as it generally causes strong antiproliferative effects. Besides, there is a more potent synergism between amygdalin and triple drug combinations. Overall, these results emphasize that amygdalin combinations in treatment of bone cancer are significant.