Recently, tremendous attentions have been paid to the fabrication of bio-based intrinsic fire-retarded epoxy resins with outstanding thermal and mechanical properties from renewable resources. Herein, the bio-based epoxy monomer of diglycidyl ether luteolin (DGEL) was synthesized via one-step method from sustainable luteolin. The biocompatible epoxy resin was manufactured via the curing reaction between DGEL and 4, 4′-diaminodiphenyl sulfone (DDS). DGEL/DDS showed higher glass transition temperature (Tg) (314.4 °C) than diglycidyl ether bisphenol A (DGEBA)/DDS (217.4 °C), demonstrating the distinguished heat resistance. Tensile testing results exhibited that DGEL/DDS possessed superior tensile strength (69.2 MPa) compared to DGEBA/DDS (57.2 MPa). Thermogravimetric analysis (TGA) illustrated that the char yield of DGEL/DDS was 44.0 wt%, much higher than that of DGEBA/DDS (11.6 wt%). In addition, DGEL/DDS passed the V-0 rating in UL-94 tests with a high limiting oxygen index (LOI) (32.5%) as well as extremely low peak heat release rate (107.5 W/g) indicating the excellent flame retardant properties. Smoke density testing results showed that the peak density of smoke for DGEL/DDS was 304.7, much lower than that for DGEBA/DDS (660.7), indicating the remarkable reduction of toxicity hazards. This work provides a facile approach for the preparation of bio-based epoxy resins with outstanding overall properties that show promising applications in high heat resistance and flame retardant fields.