Confining dual atoms (DAs) within the van der Waals gap of two-dimensional (2D) layered materials is expected to expedite the kinetic and energetic strength in catalytic process, yet is a huge challenge in atomic-scale precise assembling DAs within two adjacent layers in the 2D limit. Here, an ingenious approach is proposed to assemble DAs of Ni and Fe into the interlayer of MoS2 . While inheriting the exceptional merits of diatomic species, this interlayer-confined structure arms itself with confinement effect, displaying the more favorable adsorption strength on the confined metal active center and higher catalytic activity towards acidic water splitting, as verified by intensive research efforts of theoretical calculations and experimental measurements. Moreover, the interlayer-confined structure also renders metal DAs a protective shelter to survive in harsh acidic environment. Our findings embodied the confinement effects at the atom level, and interlayer-confined assembling of multiple species highlights a general pathway to advance interlayer-confined DAs catalysts within various 2D materials. This article is protected by copyright. All rights reserved.