Oxaliplatin is an anticancer drug used to treat colorectal and gastric cancers. In many cases, chemotherapy is discontinued due to adverse events caused by anticancer drugs. To address this challenge, we developed a sustained-release drug delivery system using polycaprolactone sheets embedded with oxaliplatin (oxaliplatin sheets) and evaluated their therapeutic potential in murine models of colon and gastric cancers. Antitumor efficacy was compared with conventional intraperitoneal administration by monitoring tumor volume, body weight, and systemic oxaliplatin concentrations over 21 days, along with histopathological assessment of tumors and hepatic tissue. Oxaliplatin sheets demonstrated superior tumor suppression, significantly reduced Ki-67 positivity, and mitotic indices. Additionally, antitumor effects and blood oxaliplatin levels were consistent regardless of implantation site. Notably, oxaliplatin sheets significantly decreased weight loss compared with intraperitoneal administration. In our analysis of liver pathology, we found that hepatic sinusoidal obstruction and hepatocellular degeneration were significantly increased after intraperitoneal administration compared with untreated mice and mice treated with oxaliplatin sheets. Furthermore, treatment with oxaliplatin sheets improved survival. Thus, our oxaliplatin sheets exhibited effective tumor control and reduced side effects, indicating their potential as a promising treatment for advanced gastric and colorectal cancers.