Selenium nanoparticles (Se NPs) were fabricated with propolis hydro-alcoholic extract and six different methods, namely, hydrothermal, microwave irradiation, ultrasonication, UV radiation, self-assembling, and conventional heating. Results indicated that antioxidant activity, turbidity, pH, and brix values of the provided hydroalcoholic propolis extract were 85.8%, 2.235% a.u., 4.1, and 3.2°Bx, respectively. Gas chromatography analysis revealed that approximately 38 bioactive compounds were detected in the provided extract within 40 min of retention time, including chalcone. Results also revealed that each method had advantage in fabrication of Se NPs compared to others, but spherical Se NPs with overall appropriate physicochemical attributes of particle size (50–60 nm), polydispersity index (0.362), zeta potential (−41.8 mV), maximum broad absorption peak (321 nm), and antioxidant activity (12.4%) were synthesized using the ultrasonication method with a frequency of 20 kHz and a power of 300 W for 10 min.