N-glycolneuraminic acid (Neu5Gc) is a sialic acid majorly found in mammalian species except for human. The irreversible mutation of CMP-Neu5Ac hydroxylase (CMAH) enzyme caused the human inability to synthesize Neu5Gc. However, anti-Neu5Gc antibodies are still produced by the human body in response to the metabolic incorporation of diet-derived Neu5Gc, especially red meat and dairy products. Neu5Gc have been found in varying quantities on some approved biotherapeutics for treatment of numerous medical ailments, leading to the debate of the potential risk or benefit of Neu5Gc in human. The effects of the interaction between anti-Neu5Gc antibodies and antigenic Neu5Gc-containing biotherapeutics in human are largely unknown and there are still many discrepancies in terms of scientific evidence. This review article discusses the current knowledge of the proposed deleterious and therapeutic role of Neu5Gc.