Designing an effective drilling mud is a critical aspect of the drilling process. A well-designed drilling mud should not only provide efficient mud hydraulics but also fulfill three important functions: enhancing mud rheology, inhibiting hydrate formation in deepwater drilling, and suppressing shale swelling when drilling through shale formations. Achieving these functions often requires the use of various additives, but these additives are often expensive, non-biodegradable, and have significant environmental impacts. To address these concerns, researchers have explored the potential applications of ionic liquids and deep eutectic solvents in drilling mud design, which have shown promising results. However, an even more environmentally friendly alternative has emerged in the form of natural deep eutectic solvents (NADES). This research focuses on an in-house-prepared NADES based on calcium chloride and glycerine, with a ratio of 1:4, prepared at 60 °C, and utilizes it as a drilling mud additive following the API 13 B-1 standards and checks its candidacy as a rheology modifier, hydrates, and shale inhibitor. The findings of the study demonstrate that the NADES-based mud significantly improves the overall yield point to plastic viscosity ratio (YP/PV) of the mud, provides good gel strength, and inhibits hydrate formation by up to 80. Additionally, it has shown an impressive 62.8 inhibition of shale swelling while allowing for 84.1 improved shale recovery. Moreover, the NADES-based mud exhibits a 28 and 25 reduction in mud filtrate and mud cake thickness, respectively, which is further supported by the results of XRD, zeta potential, and surface tension. Based on these positive outcomes, the calcium chloride�glycerine NADES-based mud is recommended as a versatile drilling mud additive suitable for various industrial applications. Furthermore, it presents a more environmentally friendly option compared to traditional additives, addressing concerns about cost, biodegradability, and environmental impact in the drilling process for an ultimate global impact. © 2023 by the authors.