Heavy-metal toxicity imposes a potential worldwide threat to the environment and humans. Cadmium, mercury, lead, and arsenic are nonessential toxic heavy metals that are most frequently involved in environmental and health hazards. Conventional chelating agents are unsuitable for subchronic and chronic heavy-metal toxicities. Scientific literature reveals that Spirulina (Arthrospira), a photosynthetic filamentous cyanobacterium that is generally known as blue-green algae, alleviates experimentally induced heavy-metal toxicity. The present review attempts to summarize such studies regarding cadmium, mercury, lead, and arsenic toxicity. A total of 58 preclinical studies demonstrate the alleviative effect of Spirulina against experimental arsenic, cadmium, lead, and mercury toxicities. Five clinical studies reported protective effects of Spirulina against arsenic toxicity in humans. Clinical studies against three heavy metals were not found in the literature. The present literature study appears to show that Spirulina possesses promising heavy-metal toxicity-ameliorative effects that are mainly attributed to its intrinsic antioxidant activity.