PurposeThis study aimed to evaluate the compositional changes and bioaccessibility of phenolics and antioxidants in propolis during in vitro digestion as well as the cytotoxic effects of digested propolis on various cancer cell lines.Design/methodology/approachSix propolis samples were obtained and subjected to in vitro oral, gastric and intestinal digestion. Both digested and undigested samples were analyzed for their total phenolic, flavonoid and antioxidant activities. Additionally, changes in phenolic composition in the in vitro digestion system were revealed by the HPLC-DAD system. The cytotoxic effects of the digested samples were assessed on lung (A549, H1299), skin (A431), liver (Hep-G2) and colon (Caco-2) cancer cells as well as on fibroblast (Bj) cells.FindingsThe mean bioaccessibility values of phenolic and flavonoid compounds were found to be less than 35 and 24%, respectively, while the TEAC and CUPRAC antioxidant results ranged between 225.08–649.04 and 398.68–1552.28 µmol TE/g, respectively. The release of p-coumaric, ferulic, 3,4-dimethoxycinnamic acids, naringenin, pinocembrin and chrysin increased progressively from the oral to the intestinal stage. The cytotoxic effects of samples on cell lines were ranked, based on IC50 results, as A431 > Hep-G2 > Caco-2 > A549 > H1299 > Bj.Originality/valuePropolis has been recognized for centuries as a natural remedy, and numerous studies have explored its bioactive components. However, no studies have previously examined the changes in the phenolic compositions of propolis samples during digestion or their cytotoxic effects on cancer cells. Therefore, this study provides novel insights and an approach to the existing literature on this topic.Graphical abstract