Antioxidant activity, gastrointestinal solubility of polyphenols and formation of different classes of Maillard reaction products (MRPs) that occurs during thermal processing of carob powder was investigated in relation to different roasting time-roasting temperature combinations applied. Principal component analysis (PCA) was used to group carob powders with the aim of proposing optimal roasting conditions for obtaining the one with the highest biological activity that can be expected after undergoing the simulation of gastrointestinal digestion. Results showed that antioxidant activity of carob powder can be significantly increased by roasting due to improved polyphenol solubility and formation of the early-stage MRPs. Fluorescent MRPs, HMF and furfural, known for their toxic properties, were the most abundant in samples roasted under more severe time/temperature conditions. Carob powder roasted at 130 °C for 30 min yielded the highest antioxidant activity and the lowest toxic MRP formation. •Carob powder (CP) antioxidant activity of is strongly affected by roasting conditions.•Polyphenols and early-stage MRPs are the main bearers of antioxidant activity in CP.•HMF and furfural are only formed under prolonged roasting at higher temperatures.•Bioaccessibility of MRPs ranged from 50 to 97% and of polyphenols from 23 to 35%.•Roasting at 130 °C for 30 min yields the highest AO and lowest toxic MRP formation.