IntroductionDietary medicinal plants are among the most sought-after topics in alternative medicine today due to their preventive and healing properties against many diseases.AimThis study aimed to extract and determine the polyphenols from indigenous plants extracts, i.e.,Mentha longifolia, M. arvensis, Tinospora cordifolia, Cymbopogon citratus, Foeniculum vulgare, Cassia absus, Camellia sinensis, Trachyspermum ammi,C. sinensisandM. arvensis, then evaluate the antioxidant, cytotoxicity, and antimicrobial properties, besides enzyme inhibition of isolated polyphenols.MethodsThe antioxidant activity was evaluated by DPPH, Superoxide radical, Hydroxyl radical (OH.), and Nitric oxide (NO.) scavenging activity; the antidiabetic activity was evaluated by enzymatic methods, and anticancer activity using MTT assay, while the antibacterial activity.ResultsThe results showed that tested medicinal plants’ polyphenolic extracts (MPPE) exhibited the most significant antioxidant activity in DPPH, hydroxyl, nitric oxide, and superoxide radical scavenging methods because of the considerable amounts of total polyphenol and flavonoid contents. UHPLC profile showed twenty-five polyphenol complexes in eight medicinal plant extracts, categorized into phenolic acids, flavonoids, and alkaloids. The main polyphenol was 3-Feroylquinic acid (1,302 mg/L), also found inM. longifolia, C.absus, andC. sinensis, has a higher phenolic content, i.e., rosmarinic acid, vanillic acid, chlorogenic acid, p-coumaric acid, ferulic acid, gallic acid, catechin, luteolin, 7-O-neohesperideside, quercetin 3,7-O-glucoside, hesperidin, rutin, quercetin, and caffeine in the range of (560–780 mg/L). At the same time, other compounds are of medium content (99–312 mg/L). The phenolics inC. sinensiswere 20–116% more abundant than those inM. longifolia,C. absus, and other medicinal plants. WhileT. cordifoliais rich in alkaloids,T. ammihas a lower content. The MTT assay against Caco-2 cells showed that polyphenolic extracts ofT. ammiandC. citratushad maximum cytotoxicity. WhileM. arvensis, C. sinensis, andF. vulgareextracts showed significant enzyme inhibition activity,C. sinensisshowed minor inhibition activity against α-amylase. Furthermore,F. vulgareandC. sinensispolyphenolic extracts showed considerable antibacterial activity againstS. aureus, B. cereus, E. coli, andS. enterica.DiscussionThe principal component analysis demonstrated clear separation among medicinal plants’ extracts based on their functional properties. These findings prove the therapeutic effectiveness of indigenous plants and highlight their importance as natural reserves of phytogenic compounds with untapped potential that needs to be discovered through advanced analytical methods.