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Abstract Cisplatin, the first platinum chemotherapy agent to obtain Food and Drug Administration (FDA) approval in 1978, is widely used for a number of cancers. However, the painful side effects stemming from systemic delivery are the inevitable limitation of cisplatin. A possible solution is regional chemotherapy using various drug delivery systems, which reduces the systemic toxicity and increases drug accumulation in the tumor. In this paper, a rice‐grain sized, ultrasonically powered, and implantable microdevice that can synthesize cisplatin in situ is presented. The microdevice produces 0.7 mg of cisplatin within 1 h under ultrasonic irradiation (400 mW cm⁻²). The effect of the microdevice‐synthesized cisplatin is evaluated using in vitro murine breast cancer cells and ex vivo liver tissue. The results suggest that cytotoxic activities of the microdevice‐mediated cisplatin delivery are significantly higher in both in vitro and ex vivo experiments. Overall, the proposed cisplatin synthesis microdevice represents a strong alternative treatment option for regional chemotherapy