Cancer is a progressive disease that is frequently encountered worldwide. The incidence of cancer is increasing with the changing living conditions around the world. The side-effect profile of existing drugs and the resistance developing in long-term use increase the need for novel drugs. In addition, cancer patients are not resistant to bacterial and fungal infections due to the suppression of the immune system during the treatment. Rather than adding a new antibacterial or antifungal drug to the current treatment plan, the fact that the drug with anticancer activity has these effects (antibacterial and antifungal) will increase the patient's quality of life. For this purpose, in this study, a series of 10 new naphthalene-chalcone derivatives were synthesized and their anticancer-antibacterial-antifungal properties were investigated. Among the compounds, compound 2j showed activity against the A549 cell line with an IC50 = 7.835 ± 0.598 μM. This compound also has antibacterial and antifungal activity. The apoptotic potential of the compound was measured by flow cytometry and showed apoptotic activity of 14.230%. The compound also showed 58.870% mitochondrial membrane potential. Compound 2j inhibited VEGFR-2 enzyme with IC50 = 0.098 ± 0.005 μM. Molecular docking studies of the compounds were carried out by in silico methods against VEGFR-2 and caspase-3 enzymes.