Propolis is a natural product, collected by honeybees Apis mellifera, from various plant sources. Propolis is extensively used in foods and beverages because it improves human health. It contains more than 300 natural compounds such as polyphenols, phenolic aldehydes, sequiterpene-quinones, coumarins, amino acids, steroids and inorganic compounds. Propolis exhibits a broad spectrum of biological and pharmacological properties such as antimicrobial, antioxidant, anti-inflammatory, immunomodulatory, antitumor, anticancer, antiulcer, hepatoprotective, cardioprotective, and neuroprotective actions. The chemical composition and beneficial properties of propolis vary greatly depending on the phytogeographical areas, seasonal collection time, and botanical source. Polyphenols found in fruits and vegetables are beginning to receive increased attention due to their vital role in protecting neural cells from oxidative stress and neuroinflammation associated with normal aging and chronic age-related diseases. Propolis is one of the most abundant sources of polyphenols (mainly flavonoids and phenolic acids). This overview is an attempt to discuss the molecular mechanism underlying the potential beneficial effects of propolis on human health and neurological diseases.