Mucus is a viscous slime that plays a vital role in protecting and lubricating biological tissues, in particular, soft epithelium interfaces such as in the stomach, intestines, and esophagus. Previous attempts to generate mucus models that mimick or simulate its characteristics have been predominantly focused on the rheological properties. This study investigates both rheological and tribological shear properties of thin films of gastric mucus from a porcine source and its mimics at compliant soft interfaces. The lubricating efficacy of biological mucus and its mimics was observed to be superior at hydrophilic tribological interfaces compared to hydrophobic ones. Facile spreading of all mucus samples at hydrophilic steel–polydimethylsiloxane (PDMS) interfaces allowed for the retainment of the lubricating films over a wide range of speed, slide/roll ratio, and external load. In contrast, poor wetting at hydrophobic PDMS–PDMS interfaces led to depletion of the mucus samples from the interface with increasing speed. Among the different mucus models investigated in this study, fluid mixtures of commercially available porcine gastric mucin (PGM) and polyacrylic acid (PAA) displayed the most persistent lubricating effects under various tribological experimental conditions. A mixture of PGM and PAA holds a high potential as mucus mimic, not only for its rheological similarity, but also for its excellent lubricity in soft compliant and hydrophilic contacts.