More healthy and sustainable food are nowadays desirable to improve human health and protect the planet’s resources. From this perspective, the aim of this study is to investigate artichoke (Cynara scolymus L.) by-products as a potential source of phenolic compounds and to use these compounds to design new fresh egg pasta formulation. Sustainable extraction was carried out using ultrasound-assisted extraction (UAE) and chemometric techniques, such as the Response Surface Methodology (RSM). UAE process parameters (temperature and time) and solvent composition (ethanol aqueous mixtures) were optimized using a three-level Box–Behnken design, in order to carry out the maximum yield in phenols. Under the optimal conditions (temperature: 60 °C; time: 60 min; solvent: 50% ethanol:water), the amount of phenolics (TPC) was 22.4 ± 0.2 mg GAE g−1 d.w., characterized mainly by dicaffeoylquinic acid (32.8 ± 0.6 mg CAE g−1 d.w.) and chlorogenic acid (14.1 ± 0.2 mg CAE g−1 d.w.). Hence, the polyphenols extract was used as an ingredient to design a new formulation of functional fresh egg pasta. Four recipes with soft wheat and semolina (P1 and P2) and with soft wheat alone (P3 and P4) were prepared. Compared with control pastas (P1 and P3), the enriched ones (P2 and P4) showed a higher polyphenol content, especially for P4 (1.86 ± 0.03 mg GAE g−1 d.w. for P1, 2.05 ± 0.02 mg GAE g−1 d.w. for P2, 1.92 ± 0.03 mg GAE g−1 d.w. for P3, 2.04 ± 0.02 mg GAE g−1 d.w. for P4). A high decrease in TPC was observed as a result of the cooking process, especially for the two control formulations (−71% for P1 and −70% for P3) in comparison with P2 (−64%) and P4 (−55%). At last, to assess the antimicrobial effect of artichoke by-products on fresh pasta and to monitor its spoilage, we used image analysis. Corresponding to a higher TPC content, P2 and P4 showed an extended shelf life of 16% and 33%, respectively, probably due to the antioxidant activity of artichoke. The new fresh egg pasta enriched with polyphenols extracted from artichoke by-products showed very good nutritional and technological characteristics, even after cooking, confirming the good potentiality of artichoke by-products in the design of new, healthy, and sustainable food products.