The combination of a bone graft material with bisphosphonates (BPs) might be advantageous for an optimal balance of material resorption and stimulation of bone formation. This study investigated the effect of β-tricalcium phosphate (β-TCP) bone grafts coated with zoledronic acid (ZOL) on osteoblast-like cells and osteoclast-like cells (OLC). As a drug carrier, the polymer poly(D,L-lactide) was used and three different concentrations of ZOL were tested. β-TCP coated with ZOL stimulated the production of osteocalcin (OC), osteoprotegerin, and sRANKL in osteoblast-like cells. The polymer coating alone caused a significant increase in collagen type 1 and OC production. OLC viability was inhibited and the tartrate-resistant acidic phosphatase isoform-5b was significantly decreased after cultivation on polymer-coated β-TCP for 12 days. The three different concentrations of ZOL decreased cell viability and no TRAPiso-5b was detectable, indicating a strong reduction of the TRAPiso-5b after 12 days in culture. After 21 days in culture, only the higher ZOL concentrations significantly reduced cell viability and TRAPiso-5b. The results of this study show that coating of β-TCP with ZOL has stimulating effects on osteoblast-like cells. Additionally, an inhibition of osteoclasts was seen. The combination of this bone grafting material with BPs might, therefore, be effective in the treatment of large bone defects.