Proper models for predicting strength parameters of reservoirs are vital to the numerical simulation and risk analysis during gas hydrate exploration. However, unlike homogeneous hydrate reservoirs, strength parameters of interlayered sediments depend on hydrate distribution modes, which remains unclear. Herein, a series of triaxial shearing tests on sediments with hydrate layered distribution are conducted to investigate variations of strength parameters and effects of sublayers. The results indicate that failure strength of whole sediments mainly depends on the high hydrate-saturated sublayer, while the cohesion is more relevant to the low hydrate-saturated layer. Besides, prediction models are proposed to estimate the failure strength through data-fitting, strength-average, and hydrate-average methods. By comparing the accuracy and applicability of these three methods, the hydrate-average method is the best way to estimate failure strength for current use. This study can provide a feasibility reference for strength estimation and risk control during natural gas hydrate development.