Photoplethysmography (PPG) signals are widely used in clinical practice as a diagnostic tool since PPG is noninvasive and inexpensive. In this article, machine learning techniques were used to improve the performance of classifiers for the detection of cardiovascular disease (CVD) from PPG signals. PPG signals occupy a large amount of memory and, hence, the signals were dimensionally reduced in the initial stage. A total of 41 subjects from the Capno database were analyzed in this study, including 20 CVD cases and 21 normal subjects. PPG signals are sampled at 200 samples per second. Therefore, 144,000 samples per patient are available. Now, a one-second-long PPG signal is considered a segment. There are 720 PPG segments per patient. For a total of 41 subjects, 29,520 segments of PPG signals are analyzed in this study. Five dimensionality reduction techniques, such as heuristic- (ABC-PSO, cuckoo clusters, and dragonfly clusters) and transformation-based techniques (Hilbert transform and nonlinear regression) were used in this research. Twelve different classifiers, such as PCA, EM, logistic regression, GMM, BLDC, firefly clusters, harmonic search, detrend fluctuation analysis, PAC Bayesian learning, KNN-PAC Bayesian, softmax discriminant classifier, and detrend with SDC were utilized to detect CVD from dimensionally reduced PPG signals. The performance of the classifiers was assessed based on their metrics, such as accuracy, performance index, error rate, and a good detection rate. The Hilbert transform techniques with the harmonic search classifier outperformed all other classifiers, with an accuracy of 98.31% and a good detection rate of 96.55%.