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Global reliability sensitivity (GRS) index under fuzzy uncertainty is defined as the mean of the absolute difference between unconditional failure credibility and conditional failure credibility, which is important to quantify the effect of fuzzy inputs on failure credibility of the structure. The solution of this index requires nested analysis of conditional failure credibility and fuzzy mean, which introduces a large amount of computation. To efficiently estimate the GRS under fuzzy uncertainty, a method combining fuzzy simulation (FS) with fuzzy first-order and second moment (FS–FFOSM) method as well as a fuzzy sequential optimization and reliability assessment (FSORA) method are proposed. Compared with the direct double-loop FS method, in which both the conditional failure credibility and the fuzzy mean are estimated by FS, the proposed FS–FFOSM uses a more efficient FFOSM method to estimate the conditional failure credibility in the inner loop, which improves the computational efficiency of estimating GRS under fuzzy uncertainty. To further improve the computational efficiency, this paper also transforms the estimation of GRS into the solution of the optimization model under the constraint of failure credibility and establishes the FSORA method to solve the optimization model. The FSORA method uses a series of cycles of deterministic optimization and inverse design point analysis corresponding to the required fuzzy reliability index by GRS to reduce the iterations, and then the computational efficiency is further improved. Several examples illustrate the computational efficiency and accuracy of the proposed methods.