Twenty-seven novel benzo[c][1,2,5]selenadiazole-5-carboxylic acid (BSCA) derivatives were designed and synthesized. Anti-proliferative activity of these structures was tested in vitro against a panel of five human cancer cell lines, including prostate (PC-3), colon (HT-29), leukemia (CCRF-CEM), lung (HTB-54) and breast (MCF-7). Four compounds (5, 6, 7 and 19) showed potent inhibitory activity with GI50 values below 10 μM in at least one of the cancer cell lines. The selectivity of these compounds was further examined in two non-malignant cell lines derived from breast (184B5) and lung (BEAS-2B). Compound 7 exhibited promising anti-proliferative activity (GI50 = 3.7 μM) in MCF-7 cells, together with high selectivity index (SI > 27.1). The induction of cell death by compound 7 was independent of the apoptotic process and it did not affect cell cycle progression either. Likewise, radical scavenging properties of the new selenadiazole derivatives were confirmed by testing their ability to scavenge DPPH radicals. Four compounds (1, 2, 8 and 9) showed potent radical scavenging activity, compound 9 being the most effective. Overall, while compound 7 was identified as the most cell growth inhibitory agent and selectively toxic to cancer cells, compound 9 proved to be the most potent antioxidant among the selenadiazole derivatives synthesized. This series of compounds can serve as an excellent scaffold to achieve new and potent antioxidant compounds useful for several diseases, i.e. cancer, neurodegenerative, heart diseases and leishmaniasis, considering the high radical scavenging activity and low toxicity showed by most of the compounds.