Herbs and aromatic plants are valuable and excellent sources of nutrients mainly used as food additives. The aim of this study was to evaluate for the first time the phytochemical constituents, the antioxidant and antimicrobial activities of five Plantago albicans extracts (PAE) (hexane, dichloromethane, acetone, ethanol and aqueous). Moreover, the phytochemical analysis outlined the significantly (p < 0.05) richness of PAE in total polyphenol content (TPC), mainly in ethanol (384.00 ± 2.00 mg GAE/g DR) and acetone (371.33 ± 1.15 mg GAE/g DR) extracts with significantly (P ≤ 0.05) high total flavonoid content (TFC), also in ethanol (219.00 ± 2.65 mg QE/g DR) and acetone (170.33 ± 1.53 mg QE/g DR) extracts, which was later confirmed by HPLC-MS spectral analysis for the most relevant extracts identifying nineteen compounds with the major one was luteolin-7-O-glucoside. The extracts with potent antioxidant activity, exhibited strong antibacterial and antifungal activities against tested microorganisms. Pearson's correlation revealed that a negative and significant correlation between the antioxidant activity (DPPH, ABTS and FRAP) and the polyphenols quantity (TPC, TFC). On the other hand, PAE displayed antibacterial effect against all the tested bacterial strains with a strong activity towards E. faecalis. Computational study including toxicological and pharmacokinetic assessment qualified and forecasted a significant drug-likeness properties. Therefore, the present study provides new findings on the use of PAE for the treatment of various disease and application in food processing industry.