Guilderland High School boasts a variety of different course levels and types to accommodate the different needs of students.

Project Lead the Way courses in various engineering subjects are offered with an opportunity to obtain credits from the Rochester Institute of Technology.

Guilderland High School offers numerous opportunities for students to take Advanced Placement examinations, as well as place a year ahead in various courses.

Additionally, Guilderland High School offers numerous Advanced Placement courses to its students.

Decision to enroll in AP courses is at the discretion of the student and his or her guidance counselor, though teacher recommendations may also be influential.

At present, AP courses available to GHS students include European History, US History, English Language, English Literature, Calculus AB, Calculus BC, Chemistry, Music Theory, Studio Art, US Government and Politics, Physics 1, and Computer Science A, and Biology, but students have been known to take the Microeconomics, Macroeconomics, Statistics, Psychology, and Human Geography exams after self-preparation and/or preparation in non-AP classes.

Producing two shows each year, a drama in the fall and a musical in the spring, the Guilderland Players, known as 'GP' by its members, is one of the largest extracurricular activities at Guilderland High School, including more than one hundred students in its cast, stage crew, and pit.

Ehlinger, a trumpetist for the Tri City Brass Quintet, is a graduate of the Crane School of Music in Potsdam, New York and George Mason University in Fairfax, Virginia.

The Wind Ensemble, traveled to Annapolis, Maryland in April 2007 for a music festival and received the award for best instrumental group.

They have also appeared at the Albany Pro Musica High School Choral Festival and on WMHT's Music for the Holidays.

In 2023, the Chamber Choir and Jazz Band performed for the opening day of Music In Our Schools Month at the State Capitol.

The school's Media Club produces a live televised news program The GHS Reporter that runs at the start of homeroom prior to the televised announcements, replays on Time Warner Cable Educational-access television cable TV Channel 16 in Guilderland, and is available to view in the Media's YouTube channel here where you can view livestreams of athletic events, Board of Education meetings, graduations, concerts, informational meetings like Admissions nights, feature segments in the GHS Reporter, skits, and the GHS Reporter itself.

Guilderland is home to one of the top cross-country programs in the Northeast, a strong tennis program, a skilled boys' soccer team that won the Class A State Championship in 1989, the 2006, 2007 and 2008 co-ed cheerleading national champions, the 2007 New York State Section II Class A Girls' lacrosse team and New York State's 2007 section 2 class AA champion baseball team.

The 2008 boys' soccer team went undefeated with 22 wins (the most in school history) on their way to their first Section II championship since 1997.

In 2005, the boys' Tennis team went 16-0 and won the Suburban Council Championship over Bethlehem High School, and in 2011, the boys' tennis Team went 11-3 and won the Suburban Council Championship over Bethlehem Highschool.

Each Year the graduating class of Guilderland High School collects a "Senior Superlative" survey to be presented in the yearbook.

Guilderland High School sponsors dozens of student-organizations, each advised and supervised by a teacher who may participate in the club's activities.