Arsenic toxicity, imposed mainly by arsenic-contaminated groundwater, is considered a critical threat to global communal health, as there is no specific and proven conventional therapy for chronic arsenic toxicity, i.e., arsenicosis, which is an insidious global public health menace affecting 50 countries. Alternative options should, therefore, be explored for the mitigation of arsenicosis. Literature survey reveals several natural compounds from plants possess significant protective efficacy against arsenic toxicity in chiefly preclinical and few clinical investigations. The studies on the ameliorative effects of plant-derived natural compounds against arsenic toxicity published in the last 25 years are collated. Forty-eight plant-based natural compounds possess alleviative effects on experimental arsenic-induced toxicity in animals, six of which have been reported to be clinically effective in humans. A potential nutraceutical or therapeutic candidate against arsenicosis for humans may thus be developed with the help of recent advancements in research in this area, along with the currently available treatments.