The discovery of fascinating ways to control and manipulate antiferromagnetic materials have garnered considerable attention as an attractive platform to explore novel spintronic phenomena and functionalities. Layered antiferromagnets (AFMs) exhibiting interesting magnetic structures can serve as an attractive starting point to establish novel functionalities down to the two-dimensional limit. In this work, we explore the magnetoresistive properties of the spin-ladder AFM TaFe1.25Te3. Magnetization studies reveal an anisotropic magnetic behavior resulting in the stabilization of a spin-flop configuration for H (10-1) plane (i.e., out-of-plane direction). Angle-dependent longitudinal and transverse magnetoresistances show an unusual anharmonic behavior. A significant anisotropic enhancement of magnetoresistance when H (10-1) plane compared to H|| (10-1) directions has been observed. The present results deepen our understanding of the magnetoresistive properties of low-dimensional layered AFMs, and point towards the possibility of utilizing these novel material systems for antiferromagnetic spintronics.