Abstract: To investigate the deterioration rules of macroscopic properties of lime-fiber modified loess under wetting-drying cycles, the variations of shear strength, disintegration coefficient and permeability coefficient of the lime-fiber modified loess are analyzed through direct shear tests, disintegration tests and permeability tests. The results show that the cementitious substances generated by lime hydration can fill the pores inside fiber reinforcement soil, enhancing soil compaction while inhibiting the development of seepage channels. After 15 wetting-drying cycles, the disintegration coefficients of fiber-reinforced loess and lime–fiber reinforced loess increase by 6.5% and 10.7%, respectively, compared with those of untreated loess. Meanwhile, their permeability coefficients increase by 8.3% and 18.2%, respectively. The deterioration rate of macroscopic properties of lime-reinforced loess gradually slows down with the increase of wetting-drying cycles. The hyperbolic model can reflect the correlation relationship between the deterioration of macroscopic properties and the number of wetting-drying cycles. The macroscopic performance of lime-fiber-reinforced loess is significantly better than that of single reinforced loess, with the final deterioration degree ranking as follows: permeability resistance > cohesion > disintegration resistance > internal friction angle. The synergistic effect of lime and fiber effectively improves the long-term stability of loess and provides experimental support for the protection of loess slopes in Northwest China.