This study analyzed the association of the sociodemographic, labor, and health conditions on the quality of life (QOL) of the periodontists in Colombia. A mixed study (explanatory sequential design) was conducted. The first quantitative phase was carried out by a cross-sectional survey (n = 187; 60.4% females). Variables: sociodemographics, labor, and health conditions, QOL (WHOQOL-BREF). Normality tests, descriptive statistics, and bivariate analyzes were performed. Factors associated with QOL were established using multivariate linear regression. A second qualitative phase with two focus groups (FGs) delved into those aspects of relevance, through qualitative content analysis and triangulation of information. The multivariate linear regression analysis showed that the factors associated with the QOL scores were in the case of men and negatively (QOL decreases): having low social support (p < 0.001), reporting poor mental health (p < 0.01). For women, QOL scores were negatively associated with low social support (p < 0.001), reporting poor general and mental health (p < 0.01), having greater stress at work (p < 0.05), having a temporary contract (p < 0.05), and living in a medium or low socioeconomic status (p < 0.05). The analysis of the FG allowed us to understand how QOL is permeated by the social context. The specialization of periodontics has generated a change in living conditions, and an adaptation to the workplace that allows them to gain recognition and a higher QOL. In conclusion, the QOL of periodontists is defined in subjective terms (standards) and related to social and labor conditions. Follow-up and evaluation strategies of the general conditions of these clinical specialists in Colombia are required.