Traditional liquid marbles (LMs), are liquid droplets encapsulated by hydrophobic particles offering special three-dimensional (3D) stereo-architectures with structurally and functionally confined environments. However, the particle armors impede optical characterization in chemical analysis and process monitoring for fluid reactions. For the first time, we manipulated the liquid–solid interface by the paradigm of liquid marbles in liquid (LMIL) strategy, in which LMs are coated by diverse particles immersed in organic mediums rendering an optically transparent micro-reactor system without compromising on its original key features. We demonstrated comparable transmittance of highly transparent liquid marble in liquid (HT-LMIL) towards naked water droplets via UV–vis absorption spectroscopic detection. Besides, its function as an oil immersion lens gives higher resolution in optical spectroscopic characterization. The high optical transparency of LMIL enables real-time and in situ monitoring of yeast cells’ proliferation and viability via layer-by-layer, encouraging them to differentiate in suspension without anchoring. Such multifaceted characteristics of HT-LMIL based platform offer optically transparent and functionally promising micro/bio-reactors with future explorations for high-throughput chemical assays.