Breast cancer is one of the most prevalent cancer types worldwide. Chemotherapy is a substantial approach in the management of breast cancer despite the occurrence of chemotherapy-associated side effects and the development of multidrug resistance in cancer cells. At this point, a variety of quinone derivatives may represent potential as possible anticancer drug candidates due to possessing structural similarity towards clinically used anticancer drugs like doxorubicin. Therefore, we investigated the cytotoxic effects of various quinone derivatives with structural diversity towards a variety of breast cancer cells. We further determined their toxicity in healthy cells to evaluate their drug capability potential. Eighteen quinone derivatives (arbutin, hydroquinone, alkannin, lapachol, lawsone, juglone, aloe-emodin, aloin, cascaroside A (8-O-β-D-glucoside of 10-C-β-D-glucosyl aloe-emodin anthrone), chrysophanol, chrysophanol-8-O-β-D-glucoside, emodin, emodin-8-O-β-D-glucoside, frangulin A (emodin-6-O-a-L-rhamnoside), physcion, rhein, sennoside A, sennoside B (sennoside A and sennoside B are stereoisomers and rhein-dianthrone diglycosides in which β-D-glucose units are bound to the OH groups of rhein anthrones at their 8th positions) were tested on MCF-7, SK-BR-3, MDA-MB-468, and MDA-MB-231 breast cancer cells and on H9c2 healthy rat cardiac myoblast cells in terms of their cytotoxicity and toxicity, respectively. The resazurin reduction assay was used to determine the cytotoxicity. Among the tested compounds, two naphthoquinone derivatives alkannin and juglone exhibited remarkable cytotoxicity on breast cancer cells and exhibited alleviated toxicity profiles on healthy cells deserving further investigation as possible drug candidates against breast cancer. Structure-activity relationships of these compounds were also evaluated and discussed. Alkannin and juglone, which are naphthoquinone derivatives isolated from natural sources, may be promising agents in the development of drug-candidate molecules with increased efficacy and safety for breast cancer.