In the present work, we have developed a greener approach to synthesize a series of novel bis(α-aminophosphonates) (bis(α-Aps)) via a microwave-mediated nano TiO2-SiO2 catalyzed Kabachnik-Fields (K-F) reaction under solvent-free conditions. An in silico molecular docking analysis was performed on all the designed molecules prior to their synthesis to get insight into their capacity to block the enzymes, α-amylase (PDB ID:3IJ8) and α-glucosidase (PDB ID:1OBB). The molecules with significant binding affinity were synthesized and spectroscopically analyzed to confirm their structure. They were screened further in vitro for their inhibitory activity on the target enzymes. When compared with the reference drug, the compounds diethyl[(2H‐1,3‐benzodioxol‐5‐yl)[(6‐{[(2H‐1,3‐benzodioxol‐5‐yl)(diethoxyphosphoryl)-methyl]amino}‐10,10‐dioxo‐9H‐10λ6‐thioxanthen‐3‐yl)amino]-methyl]phosphonate (4h), diethyl [(anthracen-9-yl)[(6-{[(anthracen-9-yl)(diethoxyphosphoryl)methyl]amino}-10,10-dioxo-9H-10λ6-thioxanthen-3-yl)amino]-methyl]phosphonate (4i) have shown greater inhibition, and diethyl{[(6‐{[(diethoxyphosphoryl)(phenyl)methyl]amino}‐10,10‐dioxo‐9H‐10λ6‐thioxanthen‐3‐yl)amino](phenyl)methyl}phosphonate (4a), diethyl {[(6-{[(diethoxyphosphoryl)(4-hydroxy-3-nitrophenyl)methyl]amino}-10,10-dioxo-9H-10λ6-thioxanthen-3-yl)amino](4-hydroxy-3-nitrophenyl)methyl}phosphonate (4e) have shown equal inhibition against the α-amylase enzyme. Compounds diethyl{[(6‐{[(diethoxyphosphoryl)(phenyl)methyl]amino}‐10,10‐dioxo‐9H‐10λ6‐thioxanthen‐3‐yl)-amino](phenyl)methyl}phosphonate (4a), diethyl[(2H‐1,3‐benzodioxol‐5‐yl)[(6‐{[(2H‐1,3‐benzodioxol‐5‐yl)(diethoxyphosphoryl)methyl]amino}‐10,10‐dioxo‐9H‐10λ6‐thioxanthen‐3‐yl)amino]methyl]phosphonate (4h), and diethyl [(anthracen-9-yl)[(6-{[(anthracen-9-yl)(diethoxyphosphoryl)methyl]amino}-10,10-dioxo-9H-10λ6-thioxanthen-3-yl)amino]-methyl]phosphonate (4i) have shown superior inhibition and diethyl{[(6‐{[(diethoxyphosphoryl)(naphthalen‐1‐yl)methyl]amino}‐10,10‐dioxo‐9H‐10λ6‐thioxanthen‐3‐yl)amino](naphthalen‐1‐yl)methyl}phosphonate (4 g) has shown equal inhibition against the α-glucosidase enzyme. All the remaining compounds displayed modest to good inhibition when compared with the reference drug, Acarbose.