In the presented study, a comparative analysis of phenolic compounds, parallel with antioxidant and antimicrobial activity of selected plants from Spanish medicinal flora was conducted. Total phenolic content, flavonoid concentrantions, antioxidant activity and antioxidant capacity, as well as antimicrobial activity were determined for methanolic extracts from 21 medicinal or potential medicinal plants sampled from eight different locations on the teritory of Spain. The phenolic content, antioxidant properties and antimicrobial activity were determined for the first time for some analyzed species. Results for total phenolic content determined using Folin-Ciocalteu reagent and expressed in term of gallic acid equivalent, GAE (mg of GA/g of extract) ranged from 35.67 to 286.18 mg of GA/g of extract. The concentrations of flavonoids determined using spectrophotometric method with aluminium chloride and expressed in terms of rutin equivalent, RuE (mg of Ru/g of extract) ranged from 31.58 to 147.34 mg of Ru/g of extract. Antioxidant activity was determined using DPPH (1,1-diphenyl-2-picrylhydrazyl radical) reagent and was expressed as IC50 (concentration of sample which is required to scavenge 50% of radicals), where values ranged from 123.80 to 14.77 μg/ml. Obtained results for antioxidant capacity evaluated using the Briggs-Rauscher oscillating reaction method ranged from 190.00 to 19.00 min. Antimicrobial activities of the studied methanol extracts were determined against three gram positive, three gram negative and two fungal strains using microdilution method. Investigated extracts exhibited variable activities with minimal inhibitory concentrations ranging from 0.01-20.00 mg/ml. A significant relation was noticed between the phenolic content, antioxidant activity analyzed through both methods and antimicrobial activity. High amounts of phenolics responsible for the good biological activity of the extracts from the tested plants is in connection with the local, zonal imposed habitat characteristics. The findings of our comparative study and interpretations of the obtained results promote the Mediterranean medicinal flora as an effective source of bioactive substances.