| Summary: | The current study aimed to evaluate the naturally occurring antimicrobial and antidiabetic potential of various <i>Echium humile</i> (<i>E. humile</i>) solvent extracts (hexane, dichloromethane, ethyl acetate, methanol and aqueous). The bioactive compounds were identified using HPLC–MS, revealing the presence of sixteen phytochemical compounds, with the most abundant being <i>p</i>-coumaric acid, followed by 4,5-di-<i>O</i>-caffeoylquinic acid, trans-ferulic acid and acacetin. Furthermore, <i>E. humile</i> extracts showed marked antimicrobial properties against human pathogen strains, with MIC values for the most relevant extracts (methanol and ethyl acetate) ranging from 0.19 to 6.25 mg/mL and 0.39 to 12.50 mg/mL, respectively. Likewise, methanol was found to be bactericidal towards <i>S. aureus</i>, <i>B. cereus</i> and <i>M. luteus</i>, fungicidal against <i>P. catenulatum</i> and <i>F. oxysporum</i> and have a bacteriostatic/fungicidal effect for the other strains. In addition, the <i>E. humile</i> methanolic extract had the greatest α-glucosidase inhibitory effect (IC<sub>50</sub> = 0.06 ± 0.29 mg/mL), which is higher than the standard drug, acarbose (IC<sub>50</sub> = 0.80 ± 1.81 mg/mL) and the aqueous extract (IC<sub>50</sub> = 0.70 ± 0.67 mg/mL). A correlation study between the major phytochemicals and the evaluated activities was investigated. Docking studies evidenced that most of the identified phenolic compounds showed strong interactions into the binding sites of <i>S. aureus</i> tyrosyl-tRNA synthetase and human lysosomal acid-α-glucosidase, confirming their suitable inhibitory effect. In summary, these results may provide rational support to explore the clinical efficacy of <i>E. humile</i> and its secondary metabolites in the treatment of dual diabetes and infections.
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