Gastric cancer (GC), particularly the undifferentiated type, is frequently associated with peritoneal metastasis, which significantly worsens prognosis due to its resistance to conventional treatments. Photodynamic therapy (PDT) is localized treatment using a photosensitizer (PS) activated by light of a specific wavelength to generate cytotoxic reactive oxygen species that induce cell death. Severe adverse events were reported from clinical trials investigating PDT for peritoneal dissemination conducted until the early 2000s, leaving its safety and clinical effectiveness unestablished. The present study explored whether "non-cytotoxic" PDT using talaporfin sodium (TS) could enhance efficacy of chemotherapeutic agents in undifferentiated GC cell line HGC27. Cell viability was evaluated with MTT assay following TS-PDT, and the synergistic effect between non-cytotoxic TS-PDT and anticancer drug SN-38 was assessed. Changes in expression of drug resistance markers were analyzed through qRT-PCR, Western blotting, and immunocytochemistry. We found that non-cytotoxic TS-PDT enhanced the efficacy of chemotherapy in the undifferentiated GC cell line and reduced the expression of C-X-C chemokine receptor type 4, a key marker associated with GC stem-like properties. These findings highlight the potential of non-cytotoxic TS-PDT as a synergistic treatment approach. We conclude that non-cytotoxic TS-PDT could enhance drug sensitivity and offers a promising therapeutic strategy for GC.