Alfalfa is an important legume forage grown worldwide and its productivity is affected by drought and salt stresses. In this work, three alfalfa germplasms with contrasting tolerances were used for unraveling the transcriptomic responses to drought and salt stresses. Twenty-one different RNA samples were extracted and sequenced using the PacBio and the Illumina platforms to obtain full-length transcriptomic profiles in response to germplasm, stress condition or tissue source (leaf, stem and root). A total of 1,124,275 and 91,378 unique isoforms and genes were obtained, respectively. Comparative analysis identified multiple transcriptional and post-transcriptional regulation mechanism, including alternative splicing events, long non-coding RNAs (lncRNAs), transcription factors, and nonsense-mediated mRNA decay events. This is the first report of a genome-wide profiling of non-coding RNAs in alfalfa. Finally, a weighted gene regulation network was generated allowing to identify master genes including transcription factors and other regulators such lncRNAs in regulation of plant response to drought and salt stresses. This research provides new insight to understand the molecular mechanisms by which drought and high salinity affect alfalfa growth and production and improves and refine the underestimated transcriptional landscape in M. sativa.