To assess the clinical periodontal, bacterial, and immunological outcomes of chloro-aluminum phthalocyanine-mediated photodynamic therapy (PDT) as an adjunct to dental scaling (DS) versus DS alone among cigarette smokers (CS) and never-smokers (NS). A total of 26 patients (13 CS and 13 NS) with clinical and radiographic diagnosis of stage-II chronic periodontitis were recruited. Each patient from both groups were subjected with two parallel therapies (split-mouth): PDT + DS (test side) and DS alone (control side). Periodontal parameters were investigated by evaluating plaque scores (PS), bleeding on probing (BOP), probing depth (PD), clinical attachment loss (CAL), and alveolar bone loss (ABL). Subgingival plaque was collected to detect and quantify Porphyromonas gingivalis and Tannerella forsythia using real-time quantitative polymerase chain reaction (RT-qPCR) assay. Gingival crevicular fluid was sampled for the quantification of interleukin (IL)-1β and tumor necrosis factor-alpha (TNF-α) using enzyme linked immunosorbent assay. All assessments were performed at baseline, 3 months, and 6 months. Bleeding on probing was significantly reduced at 6 months after PDT + DS in CS groups (p < .05). Mean PD and CAL significantly reduced after both PDT + DS and DS subgroups and among NS and CS groups (p < .05). At 6 months follow-up, the copy number of both P.gingivalis and T.forsythia remained significantly high in CS group (p < .01). Only PDT + DS subgroup in CS significantly reduced the counts of P. gingivalis and T. forsythia at 3 months and 6 months (p < .05). Only at 6 months did PDT + DS showed statistically significantly reduced IL-1β levels in the NS group (p < .01). TNF-α levels significantly reduced in CS group with PDT + DS and DS alone at both 3 months and 6 months follow-up (p < .01). Chloro-aluminum phthalocyanine-mediated PDT helped to improve the non-surgical periodontal therapy outcomes among stage-II chronic periodontitis patients among smokers and never-smokers.