The development of photoprotective agents presents a growing interest due to skin disorders, e.g., cancer. In order to obtain natural-based compounds with potential photoprotective activity, we promote the synthesis and extensive characterization of a butylchalcone derivative (E)-3-(4-butylphenyl)-1-(4-methylphenyl)-prop-2-en-1-one (BMP). Moreover, we carried out a comparative analysis of two chalcones bearing a methyl (BMP) and bromo (BBP) substituent groups (at para position), on respective electronic structures and supramolecular arrangement, using density functional theory (DFT). Through theoretical calculations carried out by DFT, it was possible to verify its antioxidant property by the mechanisms of free radical scavenging, H-atom transfer (HAT), and one-electron transfer (ET), and their stabilities. Finally, from the analysis of chalcone’s electronic transitions in the excited state calculated by the time-dependent (TD)-DFT method as well as UV-vis absorption spectra of the BMP and BBP (200–390 nm), it is possible to highlight their potential use as organic photoprotective agents.