Sj & ouml;gren's syndrome-related dry eye (SSDE) is a severe dry eye subtype characterized by significant immune cell attacks on the lacrimal gland. However, delivering immunosuppressive drugs to the lacrimal glands for SSDE therapy safely and sustainably poses significant challenges in clinical practice. Herein, a ROS-responsive microneedle patch with detachable functionality (CE-MN) is developed to enable straightforward and minimally invasive administration to the lacrimal gland area by penetrating the periocular skin. CE-MN is loaded with immunosuppressive cyclosporin A and anti-inflammatory drug epigallocatechin gallate, the latter also serving as a cross-linker for the microneedle matrix. Poly(N-isopropylacrylamide-co-butylacrylate), a temperature-sensitive polymer is utilized to fabricate separable layers that allow controlled detachment of the base from the needle, reducing patient discomfort. CE-MN is capable of modulating drug release by responding to ROS, facilitating on-demand release, and drug accumulation to the lacrimal gland. Compared to traditional eye drops, the CE-MN patch facilitated long-acting drug delivery to the lacrimal gland for more than 48 h, demonstrating potent anti-inflammatory and immunosuppressive effects in an SSDE mouse model by scavenging ROS and inhibiting the proliferation of Th1, Th17 cells, and macrophages. Overall, this long-acting microneedle patch potentially offers a novel clinical approach for treating SSDE and other ocular chronic diseases.