Hybridization has recently emerged as a promising strategy for discovering new drugs. Therefore, given the important bioactivity of isatins as well as coumarins, several new hybrids based on the isatin and coumarin nuclei were proposed, synthesized, and characterized in this study. Using a simple and modified dehydration reaction, 3-hydroxy-3-[2-oxo-2-(2-oxo-2H-chromen-3-yl)ethyl] indolin-2-one was used as the starting material for the preparation of 3-(2-oxo-2-(2-oxo-2H-chromen-3-yl)ethyli-dene) indolin-2-one (2) with high yield compared to the reported procedures. In this study, compound 2 served as a building block in preparing the targeted spiro[indole-2-one-3,4'-pyrimidin-2-one]-coumarin hybrids, in simple and eco-friendly one-pot reactions. The Infrared (IR), nuclear magnetic resonance (¹HNMR and ¹³CNMR) spectroscopic data, and elemental analyses were used to determine the compositional assignments of these prepared hybrids. Here the antimicrobial effect of four products 3-5 was determined on only two fungal strains: Penicillium notatum and Alternaria solani. The results showed no effect of these compounds on the fungi used. It was very evident that the tested fungi strains were resistant. Accordingly, further studies must be conducted on a wider range of fungal strains in the future to get more effective data in this field.