Herein, two different biologically active moieties; 2-carbaldehyde thiophene and salicylic acid hydrazide were simply combined to produce ((E)-2-hydroxy-N^/-((thiophen-2-yl)methylene)benzohydrazide) (H₂L). This hybrid ligand was used for synthesis of four lanthanide complexes (Ln³⁺ = Sm³⁺, Eu³⁺, Dy³⁺ and La³⁺) as novel potential biological agents. Sequentially, the coordination behavior of lanthanide ions with a dianionic tetradentate hydrazone ligand (OONS donation sites) was examined. The lanthanide complexes were characterized on the basis of FT-IR, ¹H-NMR and mass spectrometry as well as elemental and thermal analyses and molar conductivity. The complexes were screened for in vitro antibacterial and antifungal activity against the multidrug resistant pathogens, such as Klebsiella pneumonia, Escherichia coli, Staphylococcus aureus and Candida albicans. The antimicrobial results revealed that La³⁺ complex has a good potency against different gram positive and gram negative bacteria in comparision with different series of standard drugs. On other hand, Dy³⁺ complex demonstrate a noticeable antifungal activity against C. albican. All lanthanide complexes showed a moderate antioxidant activity with IC₅₀ (0.5 mM) except La³⁺ complex. Also, in vitro cytotoxic and growth inhibitory activities against Erlish Acities Carcinoma for all produced complexes were determined. The highest degree of cytotoxicity (IC₅₀ = 50 μM) was obtained in case of Sm³⁺ complex.