Cooperation is a relevant and controversial phenomenon in human societies. Indeed, although it is widely recognized essential for tackling social dilemmas, finding suitable policies for promoting cooperation can be arduous and expensive. More often, it is driven by pre-established schemas based on norms and punishments. To overcome this paradigm, we highlight the interplay between the influence of social interactions on networks and spontaneous self-regulating mechanisms on individuals behavior. We show that the presence of these mechanisms in a prisoner's dilemma game, may oppose the willingness of individuals to defect, thus allowing them to behave cooperatively, while interacting with others and taking conflicting decisions over time. These results are obtained by extending the Evolutionary Game Equations over Networks to account for self-regulating mechanisms. Specifically, we prove that players may partially or fully cooperate whether self-regulating mechanisms are sufficiently stronger than social pressure. The proposed model can explain unconditional cooperation (strong self-regulation) and unconditional defection (weak self-regulation). For intermediate selfregulation values, more complex behaviors are observed, such as mutual defection, recruiting (cooperate if others cooperate), exploitation of cooperators (defect if others cooperate) and altruism (cooperate if others defect). These phenomena result from dynamical transitions among different game structures, according to changes of system parameters and cooperation of neighboring players. Interestingly, we show that the topology of the network of connections among players is crucial when self-regulation, and the associated costs, are reasonably low. In particular, a population organized on a random network with a Scale-Free distribution of connections is more cooperative than on a network with an Erdös-Rényi distribution, and, in turn, with a regular one. These results highlight that social diversity, encoded within heterogeneous networks, is more effective for promoting cooperation.Cooperation in human populations is a fundamental phenomenon, which has fascinated many scientists working in different fields, such as biology, sociology, economics 1-6 , and engineering 7-9 . In biology it has been pointed out that the emergence of cooperation may be favored by the presence of kin selection, based on the altruistic behavior among relatives 10,11 . Additionally, many theoretical approaches to understand the evolution of cooperation among non-relatives are based on direct reciprocity; in this case it is assumed that individuals can adopt complex strategies that take into account the past history of their interactions with other individuals 12,13 . Although the previous ones are powerful mechanisms for the evolution of cooperation, they don't cover peculiar aspects of human behavior. Indeed, the evolution of cooperation leads to reputation building, morality judgement and complex social interactions with ever increasing cognitive demands 14 . These mechanisms...