Challenges in Mechanics of Time-Dependent Materials, Mechanics of Biological Systems and Materials, and Micro-and Nanomechanics, Volume 2 of the Proceedings of the 2021 SEM Annual Conference & Exposition on Experimental and Applied Mechanics, the second volume of four from the Conference, brings together contributions to this important area of research and engineering. The collection presents early findings and case studies on fundamental and applied aspects of Experimental Mechanics, including papers in the following general technical research areas: Characterization Across Length Scales Extreme Conditions & Environmental Effects Damage, Fatigue and Fracture Structure, Function and Performance Rate Effects in Elastomers Viscoelasticity & Viscoplasticity Research in Progress Extreme Nanomechanics In-Situ Nanomechanics Expanding Boundaries in Metrology Micro and Nanoscale Deformation MEMS for Actuation, Sensing and Characterization 1D & 2D Materials Cardiac Mechanics Cell Mechanics Biofilms and Microbe Mechanics Traumatic Brain Injury Orthopedic Biomechanics Ligaments and Soft Materials