This study was designed to compare the effects of linear periodization (LP) and undulating periodization (UP) on functional capacity, neuromuscular function, body composition, and cytokines in elderly sedentary women. We also aimed to identify the presence of high responders (HR), medium responders (MR), and low responders (LR) for irisin, interleukin-1 beta (IL-1β), toll-like receptor-4 (TLR-4), and brain-derived neurotrophic factor (BDNF) to resistance training (RT). Forty-nine elderly women were assigned to a control group, LP, and UP scheme. Functional capacity, body composition, maximal strength, irisin, TLR-4, BDNF, and IL-1β were evaluated. Both periodization models were effective in improving 45° leg press 1RM, chair-stand, arm curl, and time-up and go tests, with no significant differences in body composition and cytokines. Furthermore, HR, MR, and LR were identified for irisin, IL-1β, TLR-4, and BDNF, with differences between groups and moments. This study provides evidence that both periodization models were effective in improving functional capacity and neuromuscular function, with no effect on body composition and cytokines (probably as a consequence of the different responsiveness). Furthermore, for the first time, HR, MR, and LR were identified for irisin, IL1-β, TLR-4, and BDNF in response to RT.