On April 4, 2017, Astudillo signed a minor league deal with the Arizona Diamondbacks, and was assigned to the Reno Aces. He spent the year with the Aces and elected free agency on November 6, 2017.
On November 30, 2017, Astudillo signed a minor league deal with the Minnesota Twins and was assigned to the Rochester Red Wings. Astudillo was called up to the majors for the first time on June 29, 2018. He made his major league debut at Wrigley Field the following afternoon versus the Chicago Cubs as a defensive replacement in left field in the fifth inning, later switching to center field. In the sixth inning, he singled on a ground ball to second base to score Robbie Grossman for his first major league hit. On July 14, 2018, he made his major league pitching debut, completing the final inning of a 19–6 loss to the Tampa Bay Rays at Target Field. He allowed five runs on five hits and two home runs for a 45.00 earned run average (ERA) in his lone pitching entry of the season. Astudillo spent most of his playing time at catcher and third base and made other appearances at second base. He appeared in 30 games total for the Twins in 2018, batting .355, .371 on-base percentage, .516 slugging percentage, three home runs, 21 RBI, two walks and three strikeouts over 93 plate appearances.
