This study investigated immunomodulatory and antimetastatic properties of polysaccharides extracted from hallabong (Citrus hybrid) peel, focusing on their effects on macrophage activation. Crude polysaccharides (HPWP) were obtained through hot water extraction and ethanol precipitation from dried hallabong peel powder. Macrophages isolated from mouse peritoneum were used to evaluate cytotoxicity of HPWP against normal cells and Colon 26-M3.1 carcinoma cells. Our findings revealed no cytotoxic effects of HPWP on either normal cells or Colon 26-M3.1 carcinoma cells. Immunoactivity was assessed by measuring cytokine production, specifically IL-6 and IL-12, using ELISA. Results indicated a significant, concentration-dependent increases of cytokine levels. Tumoricidal activity of NK cells was also evaluated, demonstrating enhanced tumor cell killing induced by HPWP, in a concentration-dependent manner. This increased activity was due to HPWP’s potent antimetastatic effects, as observed in a mouse model of Colon 26-M3.1 carcinoma. In comparison with a the negative control (NC, 100%), HPWP at concentrations of 10, 100, and 1000 μg/mouse showed antimetastatic effects of 49.4%, 61.3%, and 74.3%, respectively. These effects were attributed to only NK cell activation. These findings suggest that HPWP has potential as a functional ingredient in food products aimed at enhancing immune response and inhibiting cancer metastasis.