Amygdalin - a plant-based bioactive constituent particularly abundant in bitter almond has been identified as a symbol of cyanogenic glycoside chemical organic compound which originally intended to be a medication for cancer treatment once hydrolyzed to hydrogen cyanide (HCN). Unfortunately, studies have revealed that HCN can affect normal cells in a similar way, rendering it harmless to the human body. Both in vivo and in vitro investigations are extremely controversial and make its use unsafe. An updated substantial review on the source, structure, intervention with gut microbiota, anticancer therapy, bioavailability, and microencapsulation of amygdalin was summarized. Amygdalin provided anti-tumor, anti-fibrotic, anti-atherosclerosis, anti-inflammatory, immunomodulatory, analgesic, ameliorating digestive and reproductive systems, and enhancing neurodegeneration as well as myocardial hypertrophy. Studies confirmed that toxicity of amygdalin produced by its HCN after oral ingestion. However, the intravenous route of administration was much less than the oral route, and can be avoided with an oral dosage ranging from 0.6 to 1 g daily. The diversity of gut consortium is a key factor in inducing toxicity by amygdalin. Indeed, there is no guaranteed way to point out the microbial consortium for each person and provide a safe oral dosage. Recently, the encapsulating of amygdalin using alginate–chitosan nanoparticles (ACNPs) as transporter was investigated. As an active drug delivery mechanism for regulated and constant release of amygdalin with its enhanced cytotoxic effect on cancerous cells, biocompatible and biodegradable ACNPs can be applied while protecting normal cells and tissues. In conclusion, still unproven and conflicting facts give way to a broad avenue of research for a compound that could potentially be the next stage of cancer therapy.