Honey is used since ancient time as a food and to cure many diseases. The present study investigated the chemical constituents, antioxidant and enzyme inhibition activities of natural Saudi Sidr (SH) and Talh (TH) honeys. Beside entire honey samples, ethyl acetate, ethanol and water extracts were prepared. The total polyphenolic content of SH, TH and their extracts was in the range of 2.86–7.21 and 3.80–17.33 mg gallic acid equivalents/g, respectively and the total flavonoids content was in the range of 0.05–1.17 and 0.18–2.38 mg rutin equivalents/g, respectively. Out of the 53 standards analyzed by HPLC, 27 compounds were detected with highest number of compounds identified in the ethyl acetate extract of TH (45 %, 24/53) and SH (26 %, 14/53), respectively. Quinic acid was dominant compound identified in all honey samples with the highest content determined in TH ethanol extract (4454 μg/g). The majority of tested samples possessed considerable anti‐radicals and reducing ions capacity with the ethyl acetate extract from TH exerted significantly (p<0.05) the highest activity. All honey samples did not show chelating iron metal property. Honey samples revealed variable enzyme inhibition activity with TH (entire and/or ethyl acetate extract) showed significantly (p<0.05) the highest acetylcholinesterase, butyrylcholinesterase, tyrosinase and α‐amylase inhibition activity. In conclusion, ethyl acetate is the best solvent for extraction of bioactive molecules from the two honey types. Moreover, the dark‐colored TH contained the highest number of molecules and consequently exerted the best antioxidant and enzyme inhibition activities in most assays.