Investigations of biofeedback (BF) and neurofeedback (NF) training for nicotine addiction have been long documented to lead to positive gains in smoking status, behavior and to changes in brain activity. We aimed to: (a) evaluate a multi-visit combined BF/NF intervention as an alternative smoking cessation approach, (b) validate training-induced feedback learning, and (c) document effects on resting-state functional connectivity networks (rsFCN); considering gender and degree of nicotine dependence in a longitudinal design. We analyzed clinical, behavioral, and electrophysiological data from 17 smokers who completed five BF and 20 NF sessions and three evaluation stages. Possible neuroplastic effects were explored comparing whole-brain rsFCN by phase-lag index (PLI) for different brain rhythms. PLI connections with significant change across time were investigated according to different resting-state networks (RSNs). Improvements in smoking status were observed as exhaled carbon monoxide levels, Total Oxidative Stress, and Fageström scores decreased while Vitamin E levels increased across time. BF/NF promoted gains in anxiety, self-esteem, and several aspects of cognitive performance. BF learning in temperature enhancement was observed within sessions. NF learning in theta/alpha ratio increase was achieved across baselines and within sessions. PLI network connections significantly changed across time mainly between or within visual, default mode and frontoparietal networks in theta and alpha rhythms, while beta band RSNs mostly changed significantly after BF sessions. Combined BF/NF training positively affects the clinical and behavioral status of smokers, displays benefit in smoking harm reduction, plays a neuroprotective role, leads to learning effects and to positive reorganization of RSNs across time. https://clinicaltrials.gov/ct2/show/NCT02991781.