The aim of this study was to evaluate the long-term effects of a combined periodontal treatment of scaling and root planing (SRP) and Nd:YAG laser (NDL) in chronic periodontitis (CP) patients. This was accomplished by determining the periodontal indices and the interleukin-1beta (IL-1 beta) and matrix metalloproteinase-8 (MMP-8) levels of the gingival crevicular fluid (GCF). This study was performed according to a random split-mouth-design, controlled clinical trial for sulcular debridement on 40 teeth from 20 patients with generalized moderate chronic periodontitis. The periodontal healing outcomes were compared after periodontal treatment with either SRP + NDL at 1 W (test side) or SRP (control side). Plaque index (PI), gingival index (GI), probing pocket depth (PPD), and clinical attachment level (CAL) were recorded, and samples of gingival crevicular fluid (GCF) were taken at baseline and post-therapy (3 and 9 months after treatment). The GCF samples were analyzed for IL-1 beta and MMP-8. There was postoperative improvement of all clinical parameters in both groups, but test side GI, PPD, and CAL recovery was higher than that of the control side (p < 0.05). Although levels of IL-1 beta and MMP-8 in GCF after treatment were lower in the test side than the control side, there was not a statistically significant difference (p > 0.05). In the long term, we found that SRP + NDL treatment of periodontal pockets was more effective than SRP alone in reducing PPD, CAL, GI, and GCF values.