A new N2O2‐tetradentate Schiff base ligand entitled as N,N′‐((ethane‐1,2‐diybis [oxy])bis (ethan‐2,1‐diyl))bis(3‐(4‐methoxyphenyl)prop‐2‐en‐1‐imine was prepared by direct reaction between 3‐(4‐methoxyphenyl)‐2‐propenal and 1,8‐diamino‐3,6‐dioxaoctane. After characterization of the ligand, some novel cadmium coordination compounds formulated as CdLX2 (X: Cl−, Br−, I−, N3−, SCN−and NO3−) were synthesized and characterized by physical and spectral techniques. Typically crystal structure of cadmium nitrate coordination compound was determined suggesting crystallization in monoclinic system (with space group of I2/a) and a coordination geometry of square anti‐prism around the Cd (II) ion. Moreover, CdLBr2 and CdLI2 compounds were prepared in nanostructured dimensions by sonochemical method confirmed by SEM, EDX, and XRD techniques. In continuation, thermal behavior investigation of the compounds including thermal stabilities, thermal decomposition steps, and thermo‐kinetic parameters was performed based on Coats‐Redfern equations from room temperature to 900 °C. Furthermore, all the compounds were subjected to bioassay against two Gram‐positive bacteria of Staphylococcus aureus and Bacillus subtilis, two Gram‐negative bacteria of Pseudomonas aeruginosa and Escherichia coli, and two fungal strains of Aspergillus oryzae and Candida albicans. The results showed that all the synthesized compounds act well as antimicrobial agents. DNA cleavage power of the materials was also evaluated using extracted DNA from E. coli bacterium. The cytotoxic activities of some compounds were investigated against the prostate cancer cell lines (PC3) and human umbilical vein endothelial cells (HUVEC) (as normal cells) by MTT assay and nitric oxide level evaluation method as compared with cis‐platin confirming anti‐cancer effects of them. Finally, the antioxidant properties of the N2O2‐ligand and its cadmium coordination compounds were examined by DPPH and FRAP methods suggesting all the compounds have good antioxidant activity as compared with standard samples.