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Liquid smoke, a product of the pyrolysis process, includes components such as phenol, furfural, and ketones, and has acidic characteristics. Liquid smoke from various biomass sources has been used as a natural preservative worldwide and reported to be safe in humans. As a bio-economic product, liquid smoke has human health benefits. This review analyzes and describes the health benefits of liquid smoke from various biomass sources, according to in silico, in vitro, and in vivo studies. A systematic review following PRISMA guidelines was conducted to identify published reports of liquid smoke from various biomass sources. The anti-inflammatory, anti-bacterial, anti-diabetic, wound healing, and anti-periodontitis activity of liquid smoke was analyzed. Prior research has investigated liquid smoke produced through pyrolysis of various biomass types, such as rice husks (Oryza sativa), coconut shells (Cocos nucifera L.), palm kernels (Elaeis guineensis Jacq.), cocoa pods (Theobroma cacao L.), tian op, and hickory (Carya tomentosa (Lam.) Nutt.), as well as commercial liquid smoke. Toxicity testing, and in vitro and in vivo studies, are required for the assessment of health benefits. Therapeutic benefits of liquid smoke including anti-oxidant, anti-inflammatory, anti-nociceptive, anti-bacterial, anti-fungal, and anti-viral activity have been described. Further health benefits include anti-diabetic, anti-periodontitis, wound healing, and ulcer healing activity. These findings increase the use value of liquid smoke as a natural product with human health benefits.