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This study aimed to produce stable propolis nanoparticles with a size below 100 nm, suitable for various applications in industries such as pharmaceuticals, medicine, cosmetics, food, and packaging. To achieve this, propolis solid lipid nanoparticles (PSLNs) were synthesized using the hot homogenization method, and the optimized nanoparticles were analyzed using Design Expert software. The properties of the synthesized PSLN were characterized using UV–visible spectroscopy, FTIR, XRD, PSA, TEM, and zeta potential analysis. The results indicated that PSLNs with a size range of 57 ± 15 nm remained stable in an aqueous medium at pH 7.4. HPLC analysis showed that the active ingredient of phenols and flavonoids in the extract remained stable after the formation of PSLNs. Antioxidant and antibacterial properties of the extract and nanoparticles were also evaluated. The results demonstrated that the biological properties of the extract were effectively preserved in PSLNs, Additionally, the PSLN synthesized exhibited remarkable anticancer properties against the A549 cell line and with IC50 of 0.01 mg/ml after 72 h-treatment. In conclusion, the optimized PSLNs can be utilized as antioxidant and antibacterial additives and have the potential to be used as a drug or drug carrier for the treatment of lung cancer. [ABSTRACT FROM AUTHOR]