Efficient dissolution of CO2 into the reservoir fluid is a key bottleneck in geological sequestration, where conventional injection relies on slow molecular diffusion across a planar interface. Here, we present the first systematic study demonstrating the role of microdroplet dispersions in accelerating CO2 dissolution under reservoir-relevant conditions (60 bar, 20–60 °C). By generating fine CO2 droplets in water, we observed up to a 36-fold reduction in the time to saturation compared to conventional injection without droplets. Even in saline environments, where the salting-out effect suppresses solubility, droplet generation consistently offset much of this suppression. For example, at 2.4 M NaCl, dissolved CO2 after 15 min reached 0.80 mol/kg under intense drop generation, compared to only 0.13 mol/kg without droplets. This is a significant outcome for geological carbon capture and storage, which predominantly occurs in saline formations.The effect of surface-active substances, including CTAB and its combination with cellulose nanocrystals (CNC), was also examined. In the absence of droplets, surfactant-rich interfacial layers and bulk viscosity penalties hindered dissolution, reducing dissolved CO2 from 0.88 mol/kg (pure water) to just 0.15 mol/kg (CNC + CTAB) after 60 min. Using microdroplet dispersion, however, these barriers were overcome. Dissolved CO2 increased to 1.46 mol/kg in the CNC + CTAB system; a 10-fold increase over its no-drop counterpart, demonstrating the decisive role of interfacial area in governing dissolution kinetics. However, at CTAB concentrations well above the CMC, the benefit of droplet generation was reduced, as dense interfacial layers imposed significant mass-transfer resistance, highlighting the importance of surfactant dosage.These findings demonstrate that microdroplet dispersions fundamentally shift the dissolution regime, enabling faster mass transfer and higher net CO2 uptake across salinities and fluid chemistries.