Globally, colorectal cancer ranks second in women and third in men. Hydrophilic anticancer agents have limited use in lipid systems due to their weak solubility. Therefore, this study aimed to develop oleogels based on pumpkin seed oil (R1) and hydrophilic bioactive canola extract (BCE or R2) that were extracted from canola meal by-products. BCE was effectively dispersed in oleogels through the encapsulation of BCE with various concentrations (0.08, 0.2, and 0.4%) in soy lecithin to form BCE gelling agents. Four formulations (F1 as plain, F2-F4 with different concentrations of BCE) were produced using two gelators (BCE gelling agent and beeswax). The oxidative stability, microstructure, FTIR, antioxidant activity, and time-dependent experiment were investigated. The cytotoxicity against colorectal HCT116 and Caco-2 cancer cell lines in vitro was evaluated. The anti-apoptotic PI3k and COX-2 protein expressions were also assessed. The peroxide, p-anisidine, and total oxidation values of F4 were 7.85, 26.66, and 42.35, respectively, during 60 days at 60 ± 2 °C. The antioxidant activity values of F4 were 74.40% for DPPH, 54.28% for ABTS, and 5.77 mg/g for FRAP. F4 demonstrated the highest significant cytotoxic effects on cancerous cells, particularly in the Caco-2 cells with 1.40- and 1.41-fold increases compared to R2 and the positive control doxorubicin, respectively. PI3k and COX-2 expression levels were down-regulated while iNOS activity was up-regulated in both cells, with very high down-regulation recorded for F4 in Caco-2 cells. This study developed a method for producing stable lipid products loaded with hydrophilic antioxidants that may be used as an anti-colorectal platform.